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Sample records for hla-b27 transgenic rat

  1. HLA-B27-homodimer-specific antibody modulates the expansion of pro-inflammatory T-cells in HLA-B27 transgenic rats

    Osiris Marroquin Belaunzaran; Sascha Kleber; Stefan Schauer; Martin Hausmann; Flora Nicholls; Maries Van den Broek; Sravan Payeli; Adrian Ciurea; Simon Milling; Frank Stenner; Jackie Shaw; Simon Kollnberger; Paul Bowness; Ulf Petrausch; Christoph Renner

    2015-01-01

    Objectives: HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA). HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272) and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS) patients and HLA-B27 transgenic rats. We characterized a novel B272–specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorder...

  2. Cytotoxic T-Cell-Mediated Response against Yersinia pseudotuberculosis in HLA-B27 Transgenic Rat

    Falgarone, Géraldine; Blanchard, Hervé S.; Riot, Bertrand; Simonet, Michel; Breban, Maxime

    1999-01-01

    Yersinia-induced reactive arthritis is highly associated with HLA-B27, the role of which in defense against the triggering bacteria remains unclear. The aim of this study was to examine the capacity of rats transgenic for HLA-B27 to mount a cytotoxic T-lymphocyte (CTL) response against Y. pseudotuberculosis and to determine the influence of the HLA-B27 transgene on this response. Rats transgenic for HLA-B*2705 and human β2-microglobulin of the 21-4L line, which do not spontaneously develop di...

  3. HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats.

    Osiris Marroquin Belaunzaran

    Full Text Available HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA. HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272 and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS patients and HLA-B27 transgenic rats. We characterized a novel B272-specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders.The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry.HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM. HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules.HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders.

  4. HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats.

    Phoebe Lin

    Full Text Available The HLA-B27 gene is a major risk factor for clinical diseases including ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic arthritis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has recently been shown to influence several HLA-linked diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been previously investigated. In this study, we characterize the differences in the gut microbiota mediated by the presence of the HLA-B27 gene. We identified differences in the cecal microbiota of Lewis rats transgenic for HLA-B27 and human β2-microglobulin (hβ2m, compared with wild-type Lewis rats, using biome representational in situ karyotyping (BRISK and 16S rRNA gene sequencing. 16S sequencing revealed significant differences between transgenic animals and wild type animals by principal coordinates analysis. Further analysis of the data set revealed an increase in Prevotella spp. and a decrease in Rikenellaceae relative abundance in the transgenic animals compared to the wild type animals. By BRISK analysis, species-specific differences included an increase in Bacteroides vulgatus abundance in HLA-B27/hβ2m and hβ2m compared to wild type rats. The finding that HLA-B27 is associated with altered cecal microbiota has not been shown before and can potentially provide a better understanding of the clinical diseases associated with this gene.

  5. Correlation of Cecal Microflora of HLA-B27 Transgenic Rats with Inflammatory Bowel Disease

    Onderdonk, Andrew B; Richardson, James A.; Hammer, Robert E.; Taurog, Joel D.

    1998-01-01

    Transgenic rats with a high level of expression of the human major histocompatibility complex class I molecule HLA-B27 develop chronic inflammatory bowel disease (IBD) and arthritis. Assessment of the cecal microflora showed a rise in numbers of Escherichia coli and Enterococcus spp., corresponding to the presence and severity of IBD in these rats.

  6. Lactobacillus GG prevents recurrence of colitis in HLA-B27 transgenic rats after antibiotic treatment

    Dieleman, L A; Goerres, M S; Arends, A.; Sprengers, D; Torrice, C; Hoentjen, F; Grenther, W B; Sartor, R. B.

    2003-01-01

    Background and aims: Bacteroides vulgatus induces colitis in gnotobiotic HLA-B27 transgenic (TG) rats while broad spectrum antibiotics prevent and treat colitis in specific pathogen free (SPF) TG rats although disease recurs after treatment ends. Lactobacilli treat human pouchitis and experimental colitis. We investigated if Lactobacillus rhamnosus GG (L GG) can prevent colitis in TG rats monoassociated with B vulgatus and if L GG or Lactobacillus plantarum 299v (LP 299v) can treat establishe...

  7. Transfer of the inflammatory disease of HLA-B27 transgenic rats by bone marrow engraftment

    1993-01-01

    We have previously produced lines of rats transgenic for HLA-B27 and human beta 2-microglobulin (h beta 2m) that develop a progressive inflammatory disease sharing many clinical and histologic features with the B27-associated human spondyloarthropathies, including gut and male genital inflammation, arthritis, and psoriasiform skin lesions. Other transgenic lines that express lower levels of B27 and h beta 2m remain healthy. To investigate the cellular basis for the multisystem inflammatory di...

  8. A monoclonal antibody against kininogen reduces inflammation in the HLA-B27 transgenic rat

    Keith, James C.; Sainz, Irma M.; Isordia-Salas, Irma; Pixley, Robin A.; Leathurby, Yelena; Albert, Leo M.; Colman, Robert W.

    2005-01-01

    The human leukocyte antigen B27 (HLA-B27) transgenic rat is a model of human inflammatory bowel disease, rheumatoid arthritis and psoriasis. Studies of chronic inflammation in other rat models have demonstrated activation of the kallikrein–kinin system as well as modulation by a plasma kallikrein inhibitor initiated before the onset of clinicopathologic changes or a deficiency in high-molecular-mass kininogen. Here we study the effects of monoclonal antibody C11C1, an antibody against high-mo...

  9. HLA-B27 and Human β2-Microglobulin Affect the Gut Microbiota of Transgenic Rats

    Phoebe Lin; Mary Bach; Mark Asquith; Lee, Aaron Y.; Lakshmi Akileswaran; Patrick Stauffer; Sean Davin; Yuzhen Pan; Cambronne, Eric D.; Martha Dorris; Debelius, Justine W.; Lauber, Christian L.; Gail Ackermann; Baeza, Yoshiki V.; Tejpal Gill

    2014-01-01

    The HLA-B27 gene is a major risk factor for clinical diseases including ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic arthritis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has recently been shown to influence several HLA-linked diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been previously investigated. In this study, we characterize the differences in the gut microbiota mediated by t...

  10. Supplemental Antioxidants Do Not Ameliorate Colitis Development in HLA-B27 Transgenic Rats Despite Extremely Low Glutathione Levels in Colonic Mucosa

    Schepens, M.A.A.; Vink, C.; Schonewille, A.J.; Roelofs, H.M.J.; Brummer, R.J.; Meer, van der R.; Bovee-Oudenhoven, I.M.J.

    2011-01-01

    Background: Oxidative stress is presumed to play an important role in inflammatory bowel disease (IBD). Accordingly, antioxidant supplementation might be protective. Dietary calcium inhibited colitis development in HLA-B27 transgenic rats, an animal model mimicking IBD. As antioxidants might act at

  11. Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats.

    Rath, H C; Herfarth, H H; Ikeda, J S; Grenther, W B; Hamm, T E; Balish, E; Taurog, J D; Hammer, R. E.; Wilson, K H; Sartor, R B

    1996-01-01

    Genetic and environmental factors are important in the pathogenesis of clinical and experimental chronic intestinal inflammation. We investigated the influence of normal luminal bacteria and several groups of selected bacterial strains on spontaneous gastrointestinal and systemic inflammation in HLA-B27 transgenic rats. Rats maintained germfree for 3-9 mo were compared with littermates conventionalized with specific pathogen-free bacteria. Subsequently, germfree transgenic rats were colonized...

  12. Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin: a model of human spondyloarthropathies

    1995-01-01

    Human class I major histocompatibility complex allele HLA-B27 is associated with a group of human diseases called "spondyloarthropathies." Studies on transgenic rats expressing HLA-B27 and human beta 2-microglobulin have confirmed the role of HLA-B27 in disease pathogenesis. Here we report spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin (B27+ beta 2m-/- ). In the absence of beta 2-microglobulin, B27+ beta 2m-/- animals do not express the HLA-B27 tran...

  13. Dietary calcium inhibits colitis development in HLA-B27 transgenic rats [Rattus norvegicus

    Schothorst, van E.M.; Duivenvoorde, L.P.M.

    2009-01-01

    (Submitter supplied) Background and Aims: We have shown in several controlled rat and human infection studies that dietary calcium improves intestinal resistance and strengthens the mucosal barrier. Reinforcement of gut barrier function is also relevant for inflammatory bowel disease (IBD). Therefor

  14. Chemically defined diet alters the protective properties of fructo-oligosaccharides and isomalto-oligosaccharides in HLA-B27 transgenic rats.

    Petya Koleva

    Full Text Available Non-digestible oligosaccharides (NDO were shown to reduce inflammation in experimental colitis, but it remains unclear whether microbiota changes mediate their colitis-modulating effects. This study assessed intestinal microbiota and intestinal inflammation after feeding chemically defined AIN-76A or rat chow diets, with or without supplementation with 8 g/kg body weight of fructo-oligosaccharides (FOS or isomalto-oligosaccharides (IMO. The study used HLA-B27 transgenic rats, a validated model of inflammatory bowel disease (IBD, in a factorial design with 6 treatment groups. Intestinal inflammation and intestinal microbiota were analysed after 12 weeks of treatment. FOS and IMO reduced colitis in animals fed rat chow, but exhibited no anti-inflammatory effect when added to AIN-76A diets. Both NDO induced specific but divergent microbiota changes. Bifidobacteria and Enterobacteriaceae were stimulated by FOS, whereas copy numbers of Clostridium cluster IV were decreased. In addition, higher concentrations of total short-chain fatty acids (SCFA were observed in cecal contents of rats on rat chow compared to the chemically defined diet. AIN-76A increased the relative proportions of propionate, iso-butyrate, valerate and iso-valerate irrespective of the oligosaccharide treatment. The SCFA composition, particularly the relative concentration of iso-butyrate, valerate and iso-valerate, was associated (P ≤ 0.004 and r ≥ 0.4 with increased colitis and IL-1 β concentration of the cecal mucosa. This study demonstrated that the protective effects of fibres on colitis development depend on the diet. Although diets modified specific cecal microbiota, our study indicates that these changes were not associated with colitis reduction. Intestinal inflammation was positively correlated to protein fermentation and negatively correlated with carbohydrate fermentation in the large intestine.

  15. Expression of HLA-B27 in transgenic mice is dependent on the mouse H-2D genes

    1990-01-01

    HLA-B27 transgenic mice in the context of various H-2 haplotypes were produced. A high expression of the HLA-B27 antigen was observed in mice homozygous for H-2b, H-2f, H-2s, H-2p, H-2r, and H-2k haplotypes. Mice of the H-2v haplotype expressed HLA-B27 at an intermediate level. Expression of HLA-B27 was minimal in mice of the H-2q and H-2d haplotypes. This was observed both on the B10 background and in DBA/2 or BALB/c mice. Only minimal expression of HLA-B27 could be detected in B10.PL (KuDd)...

  16. Supplemental calcium attenuates the colitis-related increase in diarrhea, intestinal permeability, and extracellular matrix breakdown in HLA-B27 transgenic rats.

    Schepens, M.A.; Schonewille, A.J.; Vink, C.; Schothorst, E.M. van; Kramer, E.; Hendriks, T.; Brummer, R.J.; Keijer, J.; Meer, R. van der; Bovee-Oudenhoven, I.M.

    2009-01-01

    We have shown in several controlled rat and human infection studies that dietary calcium improves intestinal resistance and strengthens the mucosal barrier. Reinforcement of gut barrier function may alleviate inflammatory bowel disease (IBD). Therefore, we investigated the effect of supplemental cal

  17. Rat MHC-linked peptide transporter alleles strongly influence peptide binding by HLA-B27 but not B27-associated inflammatory disease

    Simmons, W.A.; Satumtira, Nimman; Taurog, J.D. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)] [and others

    1996-02-15

    Rats transgenic for the human MHC molecule HLA-B27 were used to study the effect of two alleles, cim{sup a} and cim{sup b}, which are associated with peptide transport by the MHC-encoded Tap2 transporter, on the function of HLA-B27 as a restriction element for CTL recognition of the male H-Y minor H Ag and on the multisystem inflammatory disease characteristic of B27 transgenic rats. Anti-H-Y CTL generated in cim{sup a} B27 transgenic rats lysed male B27 cim{sup b/b} targets significantly less well than cim{sup a/a} or cim{sup a/b} targets. Addition of exogenous H-Y peptides to male B27 cim{sup b/b} targets increased susceptibility to lysis to the level of cim{sup a/a} targets sensitized with exogenous H-Y peptides. {sup 3}H-labeled peptides eluted from B27 molecules of lymphoblasts from rats of two cim{sup b} and three cim{sup a} RT1 haplotypes showed that the cim{sup b} peptide pool favors comparatively longer and/or more hydrophobic peptides. These results indicate that RT1-linked Tap2 polymorphism in the rat strongly influences peptide loading of HLA-B27. Nonetheless, the prevalence and severity of multisystem inflammatory lesions were comparable in backcross rats bearing either cim{sup a/b} or cim{sup b/b}. It thus appears either that binding of specific peptides to B27 is unimportant in the pathogenesis of B27-associated disease or that the critical peptides, unlike H-Y and many others, are not influenced by Tap transporter polymorphism. 42 refs., 6 figs., 3 tabs.

  18. Lack of expression of HLA-B27 gene in transgenic mouse trophoblast. Conserved genetic pressures underlying extra-embryonic development

    1989-01-01

    The mechanisms that regulate developmental control of the expression of MHC class I genes during generation of extra-embryonic tissues are largely unknown. In the present study, we studied the levels of transcripts of the human HLA-B27 gene in extra-embryonic tissues of transgenic mice containing the HLA-B27 (heavy chain) gene by in situ hybridization with biotinylated single-stranded RNA probes. In contrast to extra-embryonic stromal cells and embryonic tissues which contain (varying levels ...

  19. HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m.

    Khare, S D; Hansen, J.; Luthra, H S; David, C S

    1996-01-01

    MHC class I allele, HLA-B27, is strongly associated with a group of human diseases called spondyloarthropathies. Some of these diseases have an onset after an enteric or genitourinary infection. In the present study, we describe spontaneous disease in HLA-B27 transgenic mice where endogenous beta2-microglobulin (beta2m) gene was replaced with transgenic human beta2m gene. These mice showed cell surface expression of HLA-B27 similar to that of human peripheral blood mononuclear cells. In addit...

  20. HLA-B27 antigen

    ... colitis Psoriatic arthritis (arthritis associated with psoriasis) Reactive arthritis Sacroiliitis (inflammation of the sacroiliac joint) Uveitis If there are symptoms or signs of an autoimmune disease, a positive HLA-B27 test may confirm the diagnosis. However, HLA-B27 ...

  1. Complement activation and HLA-B27.

    Meri, S.; Partanen, J; Leirisalo-Repo, M; Repo, H

    1988-01-01

    The efficiency of complement activation was studied in sera from HLA-B27 positive and negative subjects (27 with previous yersinia arthritis and 35 controls). Activation of complement with zymosan induced higher mean levels of the anaphylatoxin C3a in HLA-B27 positive sera (mean (SD) 7.40 (1.66) mg/l) than in HLA-B27 negative sera (6.41 (1.79) mg/l). Similarly, higher levels of C3d,g, another C3 breakdown fragment, were obtained in HLA-B27 positive sera after Escherichia coli 0111:B4 lipopoly...

  2. HLA-B27相关前葡萄膜炎的研究进展%Advancement in the investigation of HLA-B27 associated anterior uveitis

    胡小凤; 陈巍; 卢弘

    2009-01-01

    Uveitis is an important autoimmune disease.Human leukocyte antigen (HLA)-B27-associated anterior uveitis is the most common form of anterior uveitis.HLA-B27-associated anterior uveitis has distinct ocular,systemic,and genetic features.It attacks young subjects and leads to the damage of visual function due to the recurrence and complications.However,the pathologic mechanism of HLA-B27-associated anterior uveitis is still not thoroughly understood,and effective therapy is still unavailable.There are currently many experimental researches which attamp to study the etiology and develop an effective therapy for HLA-B27 acute anterior uveitis.Thus,various animal models of acute anterior uveitis such as endotoxin-induced uveitis and HLA-B27 transgenic animals including rat and mouse are established.Different therapy regimens have been designed both in clinical trial and experimental study and aquired promising achievements.Epidemiology,pathologic mechanism,different animal models and potential new therapies such as anti-TNFα,oral associated peptides tolerance and gene therapy are overviewed.%HLA-B27阳性前葡萄膜炎是前葡萄膜炎最常见的类型,患者多为青壮年,反复发作,常引起一些并发症,严重影响视力,并可伴有其他系统性疾病.但其发病机制目前仍不清楚,尚无特效的治疗方法.近年来,建立了一些前葡萄膜炎动物模型,如内毒素诱导的前葡萄膜炎和HLA-B27转基因动物模型,并进行了一系列的研究.一些新的治疗方法在临床及动物实验中也取得了很好的疗效.就HLA-B27相关前葡萄膜炎的发病机制、流行病学、动物模型及一些新的治疗方法进行综述.

  3. Seronegative pauciarticular arthritis and HLA B27.

    Eastmond, C J; Rajah, S M; D. Tovey; Wright, V.

    1980-01-01

    Twenty-six patients with a pauciarticular arthritis have been studied clinically, radiologically and with histocompatibility typing. An increased frequency of HLA B27 was found (p = 1.87 x 10(-12)). Low back and buttock pain, Achilles tendinitis and dactylitis of the toes were more frequent in HLA-B27 positive patients. It is suggested that histocompatibility testing may be of some value in diagnosis and in the investigation of the possible 'reactive' nature of this type of arthritis.

  4. Polymorphism of HLA-B27: 105 subtypes currently known.

    Khan, Muhammad Asim

    2013-10-01

    HLA-B27 has a high degree of genetic polymorphism, with 105 known subtypes, named HLA-B*27:01 to HLA-B*27:106, encoded by 132 alleles. The most common subtypes associated with ankylosing spondylitis are HLA-B*27:05 (Caucasians), HLA-B*27:04 (Chinese), and HLA-B*27:02 (Mediterranean populations). For Chinese populations, HLA-B*27:04 is associated with a greater ankylosing spondylitis risk than HLA-B*27:05. Two subtypes, HLA-B27*06 and HLA-B27*09, seem to have no disease association. These differential disease associations of HLA-B27 subtypes, and the recent discovery that ERAP1 is associated with ankylosing spondylitis for patients with HLA-B27, have increased attempts to determine the function of HLA-B27 in disease pathogenesis by studying hemodynamic features of its protein structure, alterations of its peptidome, aberrant peptide handling, and associated molecular events. However, after 40 years we still do not fully know how HLA-B27 predisposes to ankylosing spondylitis and related spondyloarthritis. PMID:23990399

  5. Heart conduction disturbance: an HLA-B27 associated disease.

    Peeters, A J; ten Wolde, S; Sedney, M.I.; de Vries, R R; Dijkmans, B A

    1991-01-01

    In recent studies from Sweden an increased prevalence of HLA-B27 associated diseases and of HLA-B27 was found in an unselected group of men with permanently implanted pacemakers and with a heart block. Furthermore, a significantly increased prevalence of HLA-B27 was found in men with a pacemaker who had no clinical or radiological signs of HLA-B27 associated disease. To obtain more insight into the association between HLA-B27 and heart block, and the possible role of HLA-B27 in causing this b...

  6. HLA-B27 subtypes among the Chukotka native groups

    Krylov, M.Y.; Alexeeva, L.I.; Erdesz, S.; Benevolenskaya, L.I. [Akademiya Meditsinskikh Nauk SSSR, Moscow (Russian Federation). Inst. Revmatizma; Reveille, J.D.; Arnett, F.C. [Texas Univ., Houston, TX (United States). Health Science Center

    1995-12-31

    The purpose of this study was to assess the relative frequency of the known HLA-B27 subtypes in HLA-B27 positive Chukotka natives, which have higher frequencies of HLA-B27 (to 40%) and spondylarthropathies (to 2%) than the Russian Caucasian population. Using oligotyping of the polymerase-chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-B27 positive individuals were successfully typed. All had HLA-B*2705, including 4 patients with Reiter`s syndrome and 5 with ankylosing spondyloarthritis, except one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. With respect to HLA-B27 subtypes the indigenous populations from the eastern part of the Chukotka Peninsula are genetically more closely related to Caucasians than to Orientals. (author). 18 refs, 1 fig., 2 tabs.

  7. HLA-B27 Misfolding and Ankylosing Spondylitis

    Colbert, Robert A.; Tran, Tri M.; Layh-Schmitt, Gerlinde

    2013-01-01

    Understanding how HLA-B27 contributes to the pathogenesis of spondyloarthritis continues to be an important goal. Current efforts are aimed largely on three areas of investigation; peptide presentation to CD8 T cells, abnormal forms of the HLA-B27 heavy chain and their recognition by leukocyte immunoglobulin-like receptors on immune effector cells, and HLA-B27 heavy chain misfolding and intrinsic biological effects on affected cells. In this chapter we review our current understanding of the ...

  8. HLA-B27 Positivity: associated health implications

    Cox, C. L.; Gibbons, H.; Evans, P; Withers, T.; Titmus, K.

    2011-01-01

    HLA-B27 positivity makes the onset of autoimmune diseases such as uveitis, ankylosing spondylitis and Crohn's disease more likely to occur. Ankylosing spondylitis and Crohn's disease are two types of HLA-B27 positive diseases that demonstrate a direct association with uveitis. Although the possession of HLA-B27 positivity is not mandatory for autoimmune diseases such as uveitis to occur, HLA-B27 positivity not only makes it more likely but may modify the clinical picture in which a patient pr...

  9. HLA-B27 typing in the categorisation of uveitis in a HLA-B27 rich population

    Huhtinen, M; Karma, A

    2000-01-01

    AIMS—To determine whether HLA-B27 typing helps the clinician in the diagnostic examination of uveitis in a HLA-B27 rich population and also whether the clinical picture of HLA-B27 positive unilateral acute or recurrent anterior uveitis (AAU) is distinguishable from the idiopathic negative form.
METHODS—During a 3 year period 220 consecutive patients with undetermined uveitis at onset were examined in the Helsinki University Eye Clinic. HLA-B27 antigen was tested for 85% of the patients. Other...

  10. Isolated HLA-B27 associated Achilles tendinitis.

    I. Olivieri; Gemignani, G; Gherardi, S; Grassi, L.; M.L. Ciompi

    1987-01-01

    The case of a 37 year old man with a longstanding HLA-B27 associated bilateral Achilles tendinitis without seronegative spondyloarthropathy is reported. This case suggests that heel enthesopathy may for a long time be the only clinical manifestation of the HLA-B27 associated disease process.

  11. The role of HLA-B27 in inflammatory arthritis

    Lynch, Sarah Janice

    2009-01-01

    Electronic version excludes material for which permission has not been granted by the rights holder The MHC class I allele, HLA-B27, is strongly associated with a group of inflammatory arthritic conditions collectively known as spondyloarthropathies (SpA). Ankylosing spondylitis (AS) shows the strongest association with 90-95 % of patients being HLA-B27 positive. The relationship between HLA-B27 and SpA has been known for over 30 years, however despite ongoing research, the reason for thi...

  12. Enhanced neutrophil migration in vivo HLA B27 positive subjects.

    Koivuranta-Vaara, P; Repo, H; Leirisalo, M; Kiistala, U; Osterman, T; Vapaatalo, H

    1984-01-01

    Chemotaxis of polymorphonuclear leucocytes in vivo was studied in patients with previous yersinia arthritis and in healthy subjects with or without HLA B27 by means of a skin chamber technique. Irrespective of previous arthritis the number of neutrophils in the chamber media was significantly higher in HLA B27 positive subjects than in those without HLA B27. The amounts of prostaglandins E2, F2 alpha, and 6-keto-F1 alpha in the chamber media correlated positively with the corresponding cell c...

  13. Autoinflammation and HLA-B27: Beyond Antigen Presentation.

    Sibley, Cailin H

    2016-08-01

    HLA-B27 associated disorders comprise a group of inflammatory conditions which have in common an association with the HLA class I molecule, HLA-B27. Given this association, these diseases are classically considered disorders of adaptive immunity. However, mounting data are challenging this assumption and confirming that innate immunity plays a more prominent role in pathogenesis than previously suspected. In this review, the concept of autoinflammation is discussed and evidence is presented from human and animal models to support a key role for innate immunity in HLA-B27 associated disorders. PMID:27229619

  14. Bartonella henselae associated uveitis and HLA-B27

    Kerkhoff, F.T.; Rothova, A

    2000-01-01

    AIM—To investigate the frequency of HLA-B27 in patients with presumed Bartonella henselae associated uveitis and to describe the clinical characteristics of HLA-B27 positive patients with uveitis and presumed ocular bartonellosis (POB).
METHODS—The diagnosis of POB was considered in 19 patients with unexplained uveitis (except for the HLA-B27 association) and high positive IgG (titre ⩾1:900) and/or IgM (titre ⩾1:250) antibodies against B henselae. In addition to B henselae serology and HLA-B2...

  15. HLA-B27和强直性脊柱炎%HLA-B27 antigen and ankylosing spondylitis

    陶赞英; 郑明慈

    2006-01-01

    HLA-B27与强直性脊柱炎呈强相关,但它在强直性脊柱炎中作用仍不详.近年来人群中HLA-B27基因亚型的研究和人类B27转基因动物模型的建立都有力地证实了HLA-B27分子是强直性脊柱炎原发关联成分.

  16. Multiple joint tuberculosis presenting as HLA-B27 disease

    Hopkins, G. O.

    1983-01-01

    A case of multifocal osteoarticular tuberculosis in a young Caucasian male is presented. The diagnostic difficulty, compounded by slow progression of the disorder and the presence of the tissue antigen HLA-B27, is discussed.

  17. Coexisting HLA-B27 positive spondyloarthritis and polyarteritis nodosa.

    Sattar, M A

    1992-01-01

    A 38 year old woman presented with widespread polyarteritis nodosa a few years after the onset of HLA-B27 positive spondyloarthritis. The concomitant coexistence of these two disorders suggests a possible association in this genetically susceptible subject.

  18. Pathogenicity of Misfolded and Dimeric HLA-B27 Molecules

    Antoniou, Antony N.; Izabela Lenart; Guiliano, David B.

    2011-01-01

    The association between HLA-B27 and the group of autoimmune inflammatory arthritic diseases, the spondyloarthropathies (SpAs) which include ankylosing spondylitis (AS) and Reactive Arthritis (ReA), has been well established and remains the strongest association between any HLA molecule and autoimmune disease. The mechanism behind this striking association remains elusive; however animal model and biochemical data suggest that HLA-B27 misfolding may be key to understanding its association with...

  19. Invasion and persistence of Salmonella in human fibroblasts positive or negative for endogenous HLA B27

    Huppertz, H; Heesemann, J

    1997-01-01

    OBJECTIVE—Analysis of the interaction of enteropathogenic bacteria with HLA B27 transfected murine fibroblasts showed a specific influence of HLA B27 on microbial invasiveness. This possible novel mechanism for the action of HLA B27 should be verified by using endogenous HLA B27 positive and negative human fibroblasts as a model for the direct interaction of arthritogenic bacteria and host cells.
METHODS—Fibroblasts were obtained from healthy donors positive or negative for HLA B27; cultivate...

  20. Pathogenicity of Misfolded and Dimeric HLA-B27 Molecules

    Antony N. Antoniou

    2011-01-01

    Full Text Available The association between HLA-B27 and the group of autoimmune inflammatory arthritic diseases, the spondyloarthropathies (SpAs which include ankylosing spondylitis (AS and Reactive Arthritis (ReA, has been well established and remains the strongest association between any HLA molecule and autoimmune disease. The mechanism behind this striking association remains elusive; however animal model and biochemical data suggest that HLA-B27 misfolding may be key to understanding its association with the SpAs. Recent investigations have focused on the unusual biochemical structures of HLA-B27 and their potential role in SpA pathogenesis. Here we discuss how these unusual biochemical structures may participate in cellular events leading to chronic inflammation and thus disease progression.

  1. Reduction of colitis by prebiotics in HLA-1327 transgenic rats is associated with microflora changes and immunomodulation

    Hoentjen, F; Welling, GW; Harmsen, HJM; Zhang, XY; Snart, J; Tannock, GW; Lien, K; Churchill, TA; Lupicki, M; Dieleman, LA

    2005-01-01

    HLA-B27 transgenic rats develop spontaneous colitis under specific pathogen-free conditions (SPF) but germ-free rats remain disease-free, emphasizing a role for intestinal bacteria in the pathogenesis of chronic intestinal inflammation. Prebiotics are dietary substances that affect the host by stimu

  2. Aortic incompetence in HLA B27-positive juvenile arthritis.

    Kean, W F; Anastassiades, T. P.; Ford, P M

    1980-01-01

    The early onset of isolated aortic incompetence in a male child with HLA B27 and peripheral arthritis is reported. Acute anterior uveitis and lone aortic incompetence occurred at 1 and 9 months respectively after the development of the acute inflammatory arthritis. The uveitis resolved with local therapy and the arthritis remitted 10 months after the onset. There has been no recurrence of the arthritis after 10 years of close follow-up but the aortic incompetence has persisted, though it rema...

  3. HLA-B27, but not HLA-B7, immunodominance to influenza is ERAP dependent.

    Akram, Ali; Lin, Aifeng; Gracey, Eric; Streutker, Catherine J; Inman, Robert D

    2014-06-15

    Endoplasmic reticulum-associated aminopeptidase-1 (ERAP1) plays a critical role in the processing of peptides prior to binding to MHC class I molecules. In this article, we show for the first time, to our knowledge, that the HLA-B27 immunodominant influenza nucleoprotein (NP) 383-391 epitope is made as an N-terminally extended 14-mer before it is trimmed by ERAP. In the absence of ERAP, there is a significant reduction in the CTL response to the B27/NP383-391 epitope in influenza A (flu)-infected B27/ERAP(-/-) mice. With the use of tetramer staining, the number of naive CD8(+) T cells expressing TCR Vβ8.1 in B27/ERAP(-/-) transgenic mice is significantly lower than that seen in B27/ERAP(+/+) mice. HLA-B27 surface expression in naive and flu-infected B27/ERAP(-/-) mice is also lower than the expression seen for the same allele in naive and flu-infected B27/ERAP(+/+) mice. In contrast, surface expression of HLA-B7 was unaffected by the absence of ERAP in B7/ERAP(-/-) transgenic mice. The B7-restricted NP418-426 CTL response in flu-infected B7/ERAP(-/-) and B7/ERAP(+/+) mice was also similar. These results provide, to our knowledge, the first in vivo demonstration of ERAP functionally influencing host immune response in an HLA allele-specific manner. This principle has relevance to diseases such as ankylosing spondylitis, in which HLA-B27 and ERAP jointly contribute to disease predisposition. PMID:24835397

  4. Acute anterior uveitis, ankylosing spondylitis, back pain, and HLA-B27.

    Beckingsale, A. B.; Davies, J.; Gibson, J M; Rosenthal, A R

    1984-01-01

    One hundred and sixty-nine patients with acute anterior uveitis were studied for the presence of HLA-B27 tissue type, radiological evidence of ankylosing spondylitis, and a history of back pain. 60% were male; 45% were HLA-B27+. The male:female ratio in the HLA-B27+ group was the same as in the whole group. 24% had radiological evidence of ankylosing spondylitis, and, of these, 83% were HLA-B27+ while 17% were HLA-B27-. There was a definite correlation between the severity of the ankylosing s...

  5. HLA-B*27 typing by sequence specific amplification without DNA extraction.

    Sayer, D. C.; Cassell, H S; Christiansen, F. T.

    1999-01-01

    HLA-B27 appears to play a direct role in the pathogenesis of ankylosing spondylitis and almost all patients with this disease have HLA-B27. Therefore, a diagnosis of ankylosing spondylitis can virtually be excluded in the absence of HLA-B27. Many techniques have been used for HLA-B*27 typing. Of these, molecular methods are the most sensitive and specific but require extracted DNA as the testing material. A technique where HLA-B*27 is amplified directly from whole blood using sequence specifi...

  6. Prevalence of HLA-B27 in the New Zealand population: effect of age and ethnicity

    Roberts, Rebecca L; Wallace, Mary C.; Jones, Gregory T.; van Rij, Andre M.; Tony R Merriman; Harrison, Andrew; White, Douglas; Stamp, Lisa K.; Ching, Daniel; Highton, John; Stebbings, Simon M

    2013-01-01

    Introduction HLA-B27 genotyping is commonly used to support a diagnosis of ankylosing spondylitis (AS). A recent study has suggested that HLA-B27 may adversely affect longevity. The objectives of this study were to determine, for the first time, the prevalence of HLA-B27 in the New Zealand population, and to test whether HLA-B27 prevalence declines with age. Methods 117 Caucasian controls, 111 New Zealand Māori controls, and 176 AS patients were directly genotyped for HLA-B27 using PCR-SSP. T...

  7. Seasonal variation of acute anterior uveitis: differences between HLA-B27 positive and HLA-B27 negative disease.

    Ebringer, R; White, L.; McCoy, R; Tait, B

    1985-01-01

    One hundred and seventy-five consecutive patients with acute anterior uveitis (AAU) were examined over a 24-month period. There was a significantly increased incidence of AAU during the months August to December (p less than 0.05). This increase was confined predominantly to the HLA-B27 negative group of patients (p less than 0.01). There was no significant monthly difference in incidence between males and females, between patients with first or recurrent attacks, or between patients with and...

  8. HLA-B27 associated spondyloarthropathy, an autoimmune disease based on crossreactivity between bacteria and HLA-B27?

    Ringrose, J.H.

    1999-01-01

    Most autoimmune diseases are associated with certain HLA types. Therefore, spondyloarthropathies (SpA) strongly associated with HLA-B27, are also often classified as autoimmune diseases. This study questions whether SpA indeed fulfils the criteria of an autoimmune disease. The Medline database was searched for all reports between 1966 and April 1998 on the presence of autoimmune reactivity in SpA patients. This search yielded 45 articles on this subject. Only eight articles study T cell react...

  9. HLA-B27 Anterior Uveitis: Immunology and Immunopathology.

    Wakefield, Denis; Yates, William; Amjadi, Shahriar; McCluskey, Peter

    2016-08-01

    Acute anterior uveitis (AAU) is the commonest type of uveitis and HLA-B27 AAU is the most frequently recognized type of acute anterior uveitis and anterior uveitis overall. Recent evidence indicates that acute anterior uveitis is a heterogenous disease, is polygenic and is frequently associated with the spondyloarthropathies (SpA). Studies of patients with AAU and animal models of disease indicate a role for innate immunity, the IL-23 cytokine pathway and exogenous factors, in the pathogenesis of both SpA and acute anterior uveitis. Recently described genetic associations cluster around immunologic pathways, including the IL-17 and IL-23 pathways, antigen processing and presentation, and lymphocyte development and activation. Patients with ankylosing spondylitis (AS) and AAU share other genetic markers, such as ERAP-1, which show strong evidence of gene-gene interaction and point to new mechanisms of disease pathogenesis. These observations have major implications for understanding the pathogenesis of HLA-B27 diseases, such as AAU, and may lead to the development of more specific therapy for AAU. Received 6 January 2016; revised 6 February 2016; accepted 18 February 2016; published online 31 May 2016. PMID:27245590

  10. HLA B27 allele types in homogeneous groups of juvenile idiopathic arthritis patients in Latvia

    Guseinova Dinara; Lazareva Arina; Sochnevs Arturs; Zavadska Dace; Eglite Jelena; Stanevicha Valda; Shantere Ruta; Gardovska Dace

    2010-01-01

    Abstract Juvenile idiopathic arthritis (JIA) is a heterogeneous condition and therapeutic strategies vary in different JIA types. The routinely accepted practice to start with Sulphasalazine (SS) as the first line treatment in patients with HLA B27 positive JIA proves to be ineffective in a large proportion of children. Objective to investigate HLA B27 positive JIA patients clinical characteristics, determined HLA B27 allele types and their connection with antirheumatic treatment in homogenou...

  11. HLA-B27 frequency in a group of patients with psoriatic arthritis *

    Danilo Garcia Ruiz; Mário Newton Leitão de Azevedo; Omar Lupi

    2012-01-01

    BACKGROUND: HLA-B27 is associated with spondyloarthritis, a group of diseases that includes psoriatic arthritis. OBJECTIVES: To describe the HLA-B27 frequency in a group of Brazilian patients with psoriatic arthritis and correlate its presence or absence with their clinical manifestations. METHODS: Cross-sectional study with 44 psoriatic arthritis patients of a Rheumatology clinic. Demographic and social data were recorded, as were skin and joints clinical examination. HLA-B27 was tested. All...

  12. Induction of HLA-B27 heavy chain homodimer formation after activation in dendritic cells

    Santos, Susana G.; Lynch, Sarah; Campbell, Elaine C.; Antoniou, Antony N.; Simon J Powis

    2008-01-01

    Introduction Ankylosing spondylitis (AS) is a severe, chronic inflammatory arthritis, with a strong association to the human major histocompatibilty complex (MHC) class I allele human leucocyte antigen (HLA) B27. Disulfide-linked HLA-B27 heavy-chain homodimers have been implicated as novel structures involved in the aetiology of AS. We have studied the formation of HLA-B27 heavy-chain homodimers in human dendritic cells, which are key antigen-presenting cells and regulators of mammalian immun...

  13. HLA-B27: natural function and pathogenic role in spondyloarthritis

    McMichael, Andrew; Bowness, Paul

    2002-01-01

    Chapter summary The human leukocyte antigen HLA-B27 is strongly associated with development of a group of inflammatory arthritides collectively known as the spondyloarthritides. We have set out to define the natural immunological function of HLA-B27, and then to apply this knowledge to understand its pathogenic role. Human leukocyte antigen class 1 molecules bind antigenic peptides for cell surface presentation to cytotoxic T lymphocytes. HLA-B27 binds and presents peptides from influenza, HI...

  14. Ankylosing spondylitis and HLA-B27: restriction fragment length polymorphism and sequencing of an HLA-B27 allele from a patient with ankylosing spondylitis

    1993-01-01

    Two groups of patients with ankylosing spondylitis (AS) from England and Poland were examined for restriction fragment length polymorphisms (RFLPs) associated with the disease. No preferential association was found between the 9.2 kb PvuII fragment in HLA-B27 positive patients with AS compared with HLA-B27 healthy subjects as had been previously reported. In the English group, however, a 14 kb PvuII fragment was more common in HLA-B27 positive subjects with AS than in normal controls. Also 4....

  15. Mimicry of human histocompatibility HLA-B27 antigens by Klebsiella pneumoniae.

    Ogasawara, M.; Kono, D H; Yu, D T

    1986-01-01

    Anti-HLA-B27 monoclonal antibody M2, which was relatively specific for human histocompatibility antigen HLA-B27, was used to test several bacteria, some of which could potentially induce chronic arthritis in HLA-B27-positive individuals. Using the Western blot procedure, we observed positive reactions with 80,000- and 60,000-dalton antigens with one strain of Klebsiella pneumoniae. Reactivity was not observed with five other monoclonal antibodies which were not reactive with HLA-B27 antigens,...

  16. Klebsiella 'modifying factor': binding studies with HLA-B27+ and B27- lymphocytes.

    Trapani, J A; McKenzie, I. F.

    1985-01-01

    On the basis that extracts of some klebsiella organisms bind selectively to the lymphocytes of HLA-B27+ individuals and induce the appearance of new antigens, attempts were made to detect the binding of klebsiella products to HLA-B27+ and B27- lymphocytes by a number of different techniques. Firstly, blocking of the binding of two different HLA-B27 specific monoclonal antibodies to HLA-B27+ lymphocytes has been examined following exposure of the lymphocytes to a cell-free culture filtrate fro...

  17. A subset of HLA-B27 molecules contains peptides much longer than nonamers.

    Urban, R G; Chicz, R M; Lane, W S; Strominger, J.L.; Rehm, A.; Kenter, M J; Uytdehaag, F G; Ploegh, H.; Uchanska-Ziegler, B; Ziegler, A.

    1994-01-01

    An unusual monoclonal antibody (MARB4) directed against HLA-B27 that reacts with only approximately 5-20% of the cell surface HLA-B27 was used for large-scale purification of these molecules. Subsequent mass spectrometry of HLA-B27-bound peptides showed that the minor MARB4-reactive population contained peptides primarily from 900 to 4000 Da in size (approximately 8-33 amino acid residues), whereas the major HLA-B27 population contained peptides in the mass range of 900-1400...

  18. The arthritis-associated HLA-B*27:05 allele forms more cell surface B27 dimer and free heavy chain ligands for KIR3DL2 than HLA-B*27:09

    Cauli, A; Shaw, J; Giles, J.; Hatano, H; Rysnik, O; Payeli, S.; McHugh, K; Dessole, G; G. Porru; Desogus, E; Fiedler, S.; Hölper, S; CARETTE A.; Blanco-Gelaz, MA; Vacca, A.

    2013-01-01

    OBJECTIVES: HLA-B*27:05 is associated with AS whereas HLA-B*27:09 is not associated. We hypothesized that different interactions with KIR immune receptors could contribute to the difference in disease association between HLA-B*27:05 and HLAB*27:09. Thus, the objective of this study was to compare the formation of β2m-free heavy chain (FHC) including B27 dimers (B272) by HLA-B*27:05 and HLA-B*27:09 and their binding to KIR immunoreceptors. METHODS: We studied the formation of HLA-B*27:05 and H...

  19. The arthritis-associated HLA-B*27:05 allele forms more cell surface B27 dimer and free heavy chain ligands for KIR3DL2 than HLA-B*27:09.

    Cauli, A; Shaw, J; Giles, J.; Hatano, H; Rysnik, O; Payeli, S.; McHugh, K; Dessole, G; G. Porru; Desogus, E; Fiedler, S.; Hölper, S; CARETTE A.; Blanco-Gelaz, MA; Vacca, A.

    2013-01-01

    OBJECTIVES: HLA-B*27:05 is associated with AS whereas HLA-B*27:09 is not associated. We hypothesized that different interactions with KIR immune receptors could contribute to the difference in disease association between HLA-B*27:05 and HLAB*27:09. Thus, the objective of this study was to compare the formation of β2m-free heavy chain (FHC) including B27 dimers (B272) by HLA-B*27:05 and HLA-B*27:09 and their binding to KIR immunoreceptors. METHODS: We studied the formation of HLA-B*27:05 and H...

  20. THE CLINICAL SIGNIFICANCE OF ANTIGEN DETECTION OF HLA-B27%HLA-B27抗原检测的临床意义

    张向阳; 郑海萍; 门金娥

    2008-01-01

    [目的]探讨HLA-B27抗原检测的临床意义.[方法]使用流武细胞仪对350名随机人群、356名强直性脊柱炎(AS)疑似患者和70名AS患者进行HLA-B27抗原检测.[结果]随机人群、AS疑似患者和AS患者的HLA-B27阳性率分别为2.29%、45.79%和91.43%,AS疑似患者的HLA-B27阳性率显著高于随机人群(P<0.01),AS患者的HLA-B27阳性率显著高于AS疑似患者(P<0.01).AS疑似患者中,男性患者的阳性率显著高于女性患者(P<0.01),青年患者的阳性率显著高于老年患者(P<0.01).[结论]在AS疑似患者中,尤其是青年男性,开展HLA-B27抗原检测有着重要的临床意义.

  1. HLA-B27检测对强直性脊柱炎诊断的价值%Diagnostic Value of HLA- B27 for Ankylosing Spondylitis

    沈云; 程涌江; 刘光平

    2001-01-01

    [目的]评价人白细胞抗原b27(HLA-B27)对诊断强直性脊柱炎(AS)的价值.[方法]选择92例AS确诊病人作病例组,70例非AS病人为对照组,均采用美国国立卫生院(NIH)微量淋巴细胞毒试验技术定性检测其HLA-B27含量.[结果]HLA-B27检测对诊断AS的敏感性为87.0%,特异性为91.4%;随机人群试验后HLA-B27阳性的患病概率为2.57%;当患病概率为50%时,试验后HLA-B27阳性患病概率为91.01%.[结论]HLA-B27检测对AS有重要的辅助诊断价值,但不能用作AS的确诊标准.

  2. HLA - B27 polymorphism in AS patients in Shandong%山东地区AS患者HLA-B27基因多态性分析

    李钦伟; 毛永鑫; 李文超; 陈立辉

    2006-01-01

    目的凋查HLA-B27等位基因在山东地区的分布情况,研究亚犁水平的HLA-B27等位基因与AS的相关性.方法应用序列特异性引物聚合酶链反应(PCR-SSP)技术检测山东地区HLA-B27阳性AS患者中B2701~25的等位基因.结果在36例HLA-B27阳性的AS患者中,只检测到B*2704和B*2705两种业型等位基因,其中B*2704阳性13例,B*2705阳性23例,构成比分别是36.11%(13/36),63.89%(23/36).结论山东地区AS患者HLA-B27,等位基因以B*2704和B*2705为主,且B*2705最多见;不同地区、不同人群的AS患者,HLA-B27各亚型分布频率存在差异性.

  3. Gen HLA-B27: polimorfizam, evolucija, raspodjela i povezanost sa spondiloartropatijama

    Grubić, Zorana

    2006-01-01

    Povezanost HLA-B27 i ankilozantnog spondilitisa, odnosno drugih spondiloartropatija, poznata je više od trideset godina. Unatoč velikom broju radova, puno nepoznanica i pitanja još je otvoreno. U ovom su članku iznesena nova saznanja o raznovrsnosti, evoluciji, raspodjeli alela HLA-B27, kao i o hipotezama povezanosti s bolestima.

  4. Review for Disease of the Year: Epidemiology of HLA-B27 Associated Ocular Disorders.

    Kopplin, Laura J; Mount, George; Suhler, Eric B

    2016-08-01

    Acute anterior uveitis is generally recognized as the most common form of uveitis. An association with HLA-B27 is seen in approximately half of cases of acute anterior uveitis. The prevalence of HLA-B27 varies widely between ethnic populations, with an approximate 8-10% prevalence in non-Hispanic whites and lower prevalence in Mexican- (4%) and African- (2-4%) Americans. A group of systemic inflammatory diseases, the spondyloarthropathies, similarly demonstrates a strong association with HLA-B27. The strength of association varies, depending on the specific spondyloarthropathy, with the strongest association found in patients with ankylosing spondylitis. The majority of patients with HLA-B27 associated uveitis will have an underlying spondyloarthropathy. Suspicion for HLA-B27 associated uveitis should prompt a careful clinical history to assess for features of a spondyloarthropathy as the characteristics of any associated uveitis may vary. PMID:27232197

  5. Is there a common pathogenesis in aggressive periodontitis & ankylosing spondylitis in HLA-B27 patient?

    Agrawal, Neeraj; Agarwal, Kavita; Varshney, Atul; Agrawal, Navneet; Dubey, Ashutosh

    2016-05-01

    HLA-B27 is having strong association to ankylosing spondylitis (AS) and other inflammatory diseases collectively known as seronegative spondyloarthropathy. In literature, although the evidence for association between AS and periodontitis as well as AS and HLA-B27 are there but the association of aggressive periodontitis in HLA-B27 positive patient with AS are not there. We hypothesize that there may be a common pathogenesis in aggressive periodontitis and ankylosing spondylitis in HLA-B27 patient. A 27-years-old female presented with the features of generalized aggressive periodontitis and difficulty in walking. On complete medical examination, ankylosing spondylitis was diagnosed with further positive HLA-B27 phenotype and negative rheumatic factor. This report may open up a new link to explore in the pathogenesis of aggressive periodontitis. PMID:27063088

  6. PCR-SSP HLA-B27亚型检测及意义%HLA-B27 subtyping by PCR-SSP method

    张志梅; 武大林

    2004-01-01

    目的对HLA-B27进行亚型检测并探讨其临床意义.方法对38例(AS样本24例;非AS样本14例)血清学确定为HLA-B27阳性的样本采用PCR-SSP方法进行HLA-B27亚型分型.结果38例样本,PCR-SSP分型36例B27阳性,2例B27阴性,误差率为5.26%.36例B27阳性中,B*2704占77.78%(28/36例);24例AS样本与14例非AS样本B*2704所占比例统计学分析无显著差异(x2=0.321,P>0.05).结论中国汉族人HLA-B27亚型以B*2704为主,AS与HLA-B27各亚型的特异基因可能无关.PCR方法准确、实用、快捷、可靠.

  7. Search for cross-reactivity between HLA B27 and Klebsiella pneumoniae.

    Archer, J R

    1981-01-01

    HLA B27 is associated with a number of forms of arthritis, including ankylosing spondylitis. It has been suggested that the disease is caused by Klebsiella pneumoniae and that the bacterium evokes an odd immune response because it cross-reacts with HLA B27. This proposed cross-reactivity was investigated in a number of ways. The results consistently failed to confirm evidence from cross reaction, even in antisera with activity against both HLA B27-positive lymphocytes and klebsiella. It is su...

  8. Development of a PCR method to detect HLA-B27 in ankylosing spondylitis

    Nätterkvist, Ylva

    2012-01-01

    The aim of the project was to develop a PCR method to detect HLA-B27 at the Immunology Department of St. James hospital in Dublin. The HLA-B27 gene is common among patients with ankylosing spondylitis (AS). Ninety percent of patients with AS have the HLA-B27 gene and it is therefore counted as a risk factor and could be used as part of the diagnosis. Twenty-two frozen blood samples from patients with AS or suspected AS were donated from the rheumatology department at St. James hospital. PCR i...

  9. HLA B-27 Subtypes in Turkish Patients with Spondyloarthropathy and Healthy Controls

    Fatma Savran Oguz; Lale Ocal; Ali Sarper Diler; Hilmi Ozkul; Faruk Asicioglu; Esen Kasapoglu; Gokay Bozkurt; Meral Konice; Mahmut Carin

    2004-01-01

    The frequency and the distribution of HLA-B27 subtypes in spondylarthropathy (SpA) patients and controls were investigated in a sample Turkish population. B27 subtyping was performed by PCR-SSP method in two groups: 49 unrelated HLA-B27 positive Turkish patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group Criteria, and 55 HLA-B27 positive healthy controls. The frequency of HLA-B∗27 was 2.6% in the Turkish population, and B∗2705 was the predominant allel...

  10. Panuveíte em artrite indiferenciada HLA-B27 positiva Panuveitis in HLA-B27 positive undifferentiated arthritis

    Mário Sérgio Ferreira Santos; Vitor Cortizo; Cícero Ricardo Torres da Costa; Ronnielly Melo Tavares; Ricardo Eric Barros Lopes

    2008-01-01

    Entre os vários tipos de inflamação ocular associados às doenças reumatológicas, a uveíte anterior é particularmente comum nas espondiloartropatias, em especial quando associada à presença do genótipo HLA-B27. Relatou-se o caso de um paciente com artrite indiferenciada HLA-B27 positivo, complicado com panuveíte e vasculite da retina, refratária ao tratamento imunossupressor tradicional, que obteve boa resposta clínica ao uso de anti-TNF-alfa.Among the several types of ocular inflammation asso...

  11. Clinical Features and Prognosis of HLA-B27 Positive and Negative Anterior Uveitis in a Korean Population

    Park, Sung Chul; Ham, Don-Il

    2009-01-01

    Clinical features and prognosis of HLA-B27 positive anterior uveitis (AU) were assessed compared with HLA-B27 negative AU in a Korean population, based on the medical records of AU patients seen at a university hospital. Twenty-seven HLA-B27 negative, idiopathic AU patients (group I) and 55 HLA-B27 positive AU patients (group II) were studied. HLA-B27 positive group was further divided into 29 with associated systemic disease (seronegative spondyloarthropathy) (group IIA) and 26 without assoc...

  12. Functional Interaction of the Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 1 Polymorphism and HLA-B27 in Vivo*

    García-Medel, Noel; Sanz-Bravo, Alejandro; Nguyen, Dung; Galocha, Begoña; Gómez-Molina, Patricia; Martín-Esteban, Adrián; Alvarez-Navarro, Carlos; de Castro, José A. López

    2012-01-01

    The association of ERAP1 with ankylosing spondylitis (AS)1 among HLA-B27-positive individuals suggests that ERAP1 polymorphism may affect pathogenesis by altering peptide-dependent features of the HLA-B27 molecule. Comparisons of HLA-B*27:04-bound peptidomes from cells expressing different natural variants of ERAP1 revealed significant differences in the size, length, and amount of many ligands, as well as in HLA-B27 stability. Peptide analyses suggested that the mechanism of ERAP1/HLA-B27 in...

  13. 两种方法检测HLA-B27的结果分析

    廖艳秋; 王红梅; 周建华

    1999-01-01

    HLA-B27与强直性脊椎炎(AS)、Reiter病、急性前葡萄膜炎等疾病相关,我国强直性脊椎炎患者中,91%带有HLA-B27抗原,而正常人群带有HLA-B27抗原的只占6%,对于临床上怀疑为AS的患者,检查HLA-B2,有诊断及鉴别诊断的价值。过去检测HLA-B27只能依赖血清学方法,我们引进了PCR方法.对27例标本同时采用两种方法进行了检测,现将结果报告如下。

  14. HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides.

    Kidnapillai, S; Sirisena, N D; Dissanayake, V H

    2016-06-01

    This preliminary study aims to describe the HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides (SA). An anonymised database of 373 Sri Lankan patients with SA referred for HLA-B27 testing was retrospectively analysed. Eighty five (22.8%) patients were positive for the HLA-B27 allele. A male preponderance was observed among the positives. The HLA-B27 allele frequency in this sample of patients with SA was relatively low compared to published studies in other populations. Further research is needed to identify the predominant subtypes of the allele to determine which subtypes are the most prevalent in a larger sample of Sri Lankan patients with SA, and to define their association with the specific types of SA. PMID:27423748

  15. Is the HLA B27 genotype a risc faktor for psoriatic arthritis and psoriasis vulgaris?

    Zerrin Öğretmen; Merve Meliha Hız; Fatma Sılan; Şule Koşar; Öztürk Özdemir

    2014-01-01

    Backround and Design: Psoriasis is a common inflammatory dermatological disease which may be complicated with joint involvement. It has been suggested that there is an association between HLA-B27 positivity and early onset psoriasis. The purpose of the current study was to investigate the incidence of HLA-B27 positivity in psoriasis patients with arthritis. Materials and Methods: In a total of 96 patients with psoriasis, age of onset, family history, and Psoriasis Area and Severity Index (...

  16. Prevalence of HLA-B27 antigen in patients with juvenile idiopathic arthritis

    Żuber, Zbigniew; Turowska-Heydel, Dorota; Sobczyk, Małgorzata; Chudek, Jerzy

    2015-01-01

    Introduction Human leukocyte antigen B27 (HLA-B27) is considered as a risk factor for development of juvenile idiopathic arthritis (JIA). The aim of this study was to analyse the prevalence of HLA-B27 antigen in JIA categories and its influence on disease onset and response to conventional therapy. Material and methods The retrospective analysis included 461 unselected children with JIA hospitalized in a single reference rheumatology centre between July 2007 and June 2012. The diagnosis was b...

  17. HLA B27 allele types in homogeneous groups of juvenile idiopathic arthritis patients in Latvia

    Guseinova Dinara

    2010-10-01

    Full Text Available Abstract Juvenile idiopathic arthritis (JIA is a heterogeneous condition and therapeutic strategies vary in different JIA types. The routinely accepted practice to start with Sulphasalazine (SS as the first line treatment in patients with HLA B27 positive JIA proves to be ineffective in a large proportion of children. Objective to investigate HLA B27 positive JIA patients clinical characteristics, determined HLA B27 allele types and their connection with antirheumatic treatment in homogenous patient groups. Materials and methods 56 patients diagnosed with JIA and observed over the period 2006 to 2009 included in the study. HLAB27 allele types were determined using PCR method. Results In HLA B27 positive JIA patients mean disease onset was 12.34 ± 3.3 years. Most common (44% JIA type was enthesitis related arthritis. Positive response to the treatment with SS was found in 32% of patients, Methotrexate (MTX - in 43%, combined treatment - SS with MTX was effective in 12.5%. 12.5% of patients required combination MTX with Enbrel. Eight HLA B27 allele types were found in JIA patients in Latvia: *2702, *2703, *2704, *2705, *2710, *2715, *2717, *2728. The most common was *2705 - in 55% of cases. Among all the patients enthesitis related arthritis most commonly occurred in patients with HLAB*2705 allele (OR = 2.01, p Conclusions There are 8 different HLA B27 alleles in JIA patients in Latvia and the most common is *2705, but in order to assert them to be disease associated alleles, more extensive studies are needed, including control group of HLA B27 positive healthy individuals. Standard treatment approach with SS proves to be unsatisfactory in the majority of JIA patients. To improve children's quality of life achieving rapid disease control, the first line treatment in HLA B27 positive patients should be MTX. In order to start with the most appropriate drug it is necessary to determine HLAB 27 type at the onset of disease.

  18. Prevalence of HLA-B27 in Patients with Ankylosing Spondylitis in Qatar

    M. H. Abdelrahman; Mahdy, S.; I. A. Khanjar; A. M. Siam; H. A. Malallah; S. A. Al-Emadi; Sarakbi, H. A.; M. Hammoudeh

    2012-01-01

    Background and Objectives. The human leukocyte antigen HLA-B27 is a class 1 antigen of the major histocompatibility complex and is strongly associated with ankylosing spondylitis (AS). The purpose of the present study is to investigate the distribution of HLA-B27 in patients with AS of different ethnic groups in Qatar. Design and Setting. Study design was cross-sectional and the setting was rheumatology clinics of Hamad General Hospital in Qatar where most of ankylosing spondylitis patien...

  19. Panuveíte em artrite indiferenciada HLA-B27 positiva Panuveitis in HLA-B27 positive undifferentiated arthritis

    Mário Sérgio Ferreira Santos

    2008-10-01

    Full Text Available Entre os vários tipos de inflamação ocular associados às doenças reumatológicas, a uveíte anterior é particularmente comum nas espondiloartropatias, em especial quando associada à presença do genótipo HLA-B27. Relatou-se o caso de um paciente com artrite indiferenciada HLA-B27 positivo, complicado com panuveíte e vasculite da retina, refratária ao tratamento imunossupressor tradicional, que obteve boa resposta clínica ao uso de anti-TNF-alfa.Among the several types of ocular inflammation associated to the rheumatic diseases, anterior uveitis is particularly common in the spondyloarthropathies, especially when associated to the presence of the HLA-B27 genotype. We report the case of HLA-B27 positive patient with undifferentiated arthritis, complicated with panuveitis and retinal vasculitis, that was refractory to the traditional imunossupressive treatment, and had a good clinical response with anti-TNF-alpha therapy.

  20. HLA-B27在门诊疑似AS诊断中的意义

    杨栋梁; 邢卫高

    2012-01-01

    目的讨论门诊疑似强制性脊柱炎(AS)诊断中HLA-B27基因检测的意义。方法对门诊疑似诊断为AS的889例患者的HLA-B27阳性率、患者性别和初诊年龄进行统计分析,并与同期随机采集的506例健康人的HLA-B27阳性率进行比较。结果 889例门诊疑似AS患者中HLA-B27阳性率为44.77%(398/889),其中男性患者的HLA-B27阳性率47.55%(339/713)与女性患者的35.52%(59/176)相比,差异具有显著统计学意义(χ2=11.23,P<0.01);对照组中HLA-B27阳性率为4.15%(21/506),与疑似AS患者的阳性率相比,呈显著统计学差异(χ2=253.18,P<0.001);男性患者发病高峰为11-20岁,而女性患者则为31-40岁。结论疑似AS患者就诊时检测HLA-B27有助于提高初诊患者诊断率,可作为鉴别诊断的重要指标。

  1. HLA-B27在门诊疑似AS诊断中的意义

    杨栋梁; 邢卫高

    2012-01-01

    目的 讨论门诊疑似强制性脊柱炎(AS)诊断中HLA-B27基因检测的意义.方法 对门诊疑似诊断为AS的889例患者的HLA-B27阳性率、患者性别和初诊年龄进行统计分析,并与同期随机采集的506例健康人的HLA-B27阳性率进行比较.结果 889例门诊疑似AS患者中HLA-B27阳性率为44.77%(398/889),其中男性患者的HLA-B27阳性率47.55%(339/713)与女性患者的35.52%(59/176)相比,差异具有显著统计学意义(χ2=11.23,P<0.01);对照组中HLA-B27阳性率为4.15%(21/506),与疑似AS患者的阳性率相比,呈显著统计学差异(χ2=253.18,P<0.001);男性患者发病高峰为11-20岁,而女性患者则为31-40岁.结论 疑似AS患者就诊时检测HLA-B27有助于提高初诊患者诊断率,可作为鉴别诊断的重要指标.

  2. 相对定量检测HLA-B27 mRNA表达水平的方法建立%Establishment of a method for relatively quantitative measurement of HLA-B27 mRNA

    王静成; 王晓玲; 费文勇; 郭开今; 王强; 王骅; 陈伟华

    2009-01-01

    Objective To establish a method for relatively quantitative measurement of HLA-B27 mRNA.Methods Totally 27 cases of peripheral venous blood samples were collected from patients with ankylosing spondylitis,including 22 cases from the patients with HLA-B27 positive and 5 cases with HLA-B27 negative.Total RNA from the venous blood samples was extracted,and then the expression level of HLA-B27 mRNA was quantitatively detected by using reverse transcription polymerase chain reaction(RT-PCR).Results The expression level of HLA-B27 mRNA was higher in patients with HLA-B27 positive(n=22;1.16-37.01,mean value was 7.77)than that in patients with HLA-B27 negative(n=5;mean value was 1.19,close to that of healthy control group).Conclusion Relatively quantitative measurement of HLA-B27 mRNA is helpful for monitoring of ankylosing spondylitis.%目的 建立检测HLA-B27 mRNA表达水平的相对定量的方法.方法 筛选未经治疗的AS患者外周静脉血27例,其中HLA-B27阳性患者22例,HLA-B27阴性患者5例,对标本进行Total RNA提取.然后用RT-PCR方法进行HLA-B27反转录及相对定量.结果 22例HLA-B27阳性AS患者有着相对较高的HLA-B27 mRNA表达水平,最低值为1.16,最高值为37.01,均值为7.77.5例HLA-B27阴性AS患者均值为1.19,接近于HLA-B27阴性健康对照组.结论 检测外周静脉血HLA-B27 mRNA表达水平对检测AS是一种有效可行的方法.

  3. Is the HLA B27 genotype a risc faktor for psoriatic arthritis and psoriasis vulgaris?

    Zerrin Öğretmen

    2014-09-01

    Full Text Available Backround and Design: Psoriasis is a common inflammatory dermatological disease which may be complicated with joint involvement. It has been suggested that there is an association between HLA-B27 positivity and early onset psoriasis. The purpose of the current study was to investigate the incidence of HLA-B27 positivity in psoriasis patients with arthritis. Materials and Methods: In a total of 96 patients with psoriasis, age of onset, family history, and Psoriasis Area and Severity Index (PASI values were recorded. The patients were evaluated with regard to physical examination (presence of arthritis, acute phase reactants, HLA-B27 positivity and joint radiographs. Control group comprised of 100 randomly selected healthy individuals. Results: Thirty (31.250% patients were with psoriasis alone, 66 (68.75% were with the findings of psoriasis and arthritis. Of the 66 patients, 17 (17.708% were symptomatic (clinical and radiologic findings and 49 (51.042% subjects were asymptomatic (radiologic findings only. Nine patients (6 with psoriasis only and 3 with psoriatic arthritis and 2 healthy controls were positive for HLA-B27. Conclusion: To carry HLA-B27 antigen increased the risk of psoriasis with an OR of 5.06, and clinically proven psoriatic arthritis with an OR of 10.5 compared to healthy controls. These results need confirmation in a larger group of patients with the inclusion of proper positive and healthy controls.

  4. Association between Polymorphism of the Vitamin D Metabolism Gene CYP27B1 and HLA-B27-Associated Uveitis. Is a State of Relative Immunodeficiency Pathogenic in HLA B27-Positive Uveitis?

    Gernot Steinwender; Ewald Lindner; Martin Weger; Sophie Plainer; Wilfried Renner; Navid Ardjomand; Yosuf El-Shabrawi

    2013-01-01

    OBJECTIVE: Polymorphisms of the vitamin D metabolism gene CYP27B1 showed associations with multiple autoimmune diseases. The aim of this study was to investigate a possible association between the rs703842 A>G polymorphism of the CYP27B1 gene and HLA-B27-associated uveitis. DESIGN: One hundred fifty-nine patients with HLA-B27-associated uveitis, 138 HLA-B27-negative controls and 100 HLA-B27-positive controls were recruited for this retrospective case-control study. Main outcome parameters wer...

  5. A Survey on the Frequency of HLA-B27 in Patients Engaged With Seronegative Spondyloarthropathies in Kashan, Iran

    Kamal Esalat-Manesh; Mohsen Taghadosi; Abas Arj

    2015-01-01

    Background: Seronegative Spondyloarthropathies (SNSAs) are referred to a group of diseases with same clinical and genetic features. Objectives: Due to lack of data about HLA-B27 prevalence in patient with SNSA in Kashan this study was conducted to determine the status of HLA-B27 in these patients. Patients and Methods: This cross sectional study was conducted on 294 patients suffered from SNSA. Presence or absence of HLA-B27 was checked by serological method using Greener kit. Res...

  6. The radiographic features of rheumatoid arthritis in HLA-B27-positive patients

    Rundback, J.H. (Dept. of Radiology, Beth Israel Medical Center, New York, NY (United States)); Rosenberg, Z.S. (Dept. of Radiology, Hospital for Joint Diseases, Orthopaedic Inst., New York, NY (United States)); Solomon, G. (Dept. of Rheumatology, Hospital for Joint Diseases, Orthopaedic Institute, New York, NY (United States))

    1993-05-01

    Radiographs were reviewed in a group of nine patients with classical seropositive rheumatoid arthritis who on tissue typing were found to express the class I HLA-B27 allele. Radiographs were analyzed with regard to whether or not they demonstrated radiographic features of (1) classical rheumatoid arthritis, (2) seronegative arthritis, or (3) mixed features of rheumatoid and seronegative arthritis. Five patients (55%) displayed radiographic features consistent with a diagnosis of rheumatoid arthritis, two patients (22%) showed radiographic features of seronegative disorder (periostitis and sacroiliitis), and two patients (22%) showed a mixed picture with evidence of both rheumatoid arthritis and a seronegative disorder. Thus, the HLA-B27 allele contributed to the radiographic features in 44% of patients with rheumatoid arthritis and associated HLA-B27. Thus, the wide range of findings in our population indicates that the radiographic attributes are not specific enough to constitute a unique subpopulation of patients with rheumatoid arthritis. (orig.)

  7. The radiographic features of rheumatoid arthritis in HLA-B27-positive patients

    Radiographs were reviewed in a group of nine patients with classical seropositive rheumatoid arthritis who on tissue typing were found to express the class I HLA-B27 allele. Radiographs were analyzed with regard to whether or not they demonstrated radiographic features of (1) classical rheumatoid arthritis, (2) seronegative arthritis, or (3) mixed features of rheumatoid and seronegative arthritis. Five patients (55%) displayed radiographic features consistent with a diagnosis of rheumatoid arthritis, two patients (22%) showed radiographic features of seronegative disorder (periostitis and sacroiliitis), and two patients (22%) showed a mixed picture with evidence of both rheumatoid arthritis and a seronegative disorder. Thus, the HLA-B27 allele contributed to the radiographic features in 44% of patients with rheumatoid arthritis and associated HLA-B27. Thus, the wide range of findings in our population indicates that the radiographic attributes are not specific enough to constitute a unique subpopulation of patients with rheumatoid arthritis. (orig.)

  8. HLA-B27 detection – comparison of genetic sequence-based method and flow cytometry assay

    Skalska, Urszula; Kozakiewicz, Anna; Maśliński, Włodzimierz; Jurkowska, Monika

    2015-01-01

    Objectives The presence of human leukocyte antigen B27 (HLA-B27) is strongly associated with ankylosing spondylitis. HLA-B27 testing is routinely applied in the diagnosis of this disease. The aim of the present study was to compare two methods of HLA-B27 detection – a genetic sequence-based method and a flow cytometry assay. Material and methods Peripheral blood was obtained from 300 individuals with suspected spondyloarthropathy. Expression of HLA-B27 on the T cell surface was analysed by fl...

  9. HLA-B27 Selects for Rare Escape Mutations that Significantly Impair Hepatitis C Virus Replication and Require Compensatory Mutations

    Neumann-Haefelin, Christoph; Oniangue-Ndza, Cesar; Kuntzen, Thomas; Schmidt, Julia; Nitschke, Katja; Sidney, John; Caillet-Saguy, Célia; Binder, Marco; Kersting, Nadine; Kemper, Michael W.; Power, Karen A.; Ingber, Susan; Reyor, Laura L.; Hills-Evans, Kelsey; Kim, Arthur Y.

    2011-01-01

    HLA-B27 is associated with spontaneous viral clearance in hepatitis C virus (HCV) infection. Viral escape within the immunodominant HLA-B27 restricted HCV-specific CD8+ T cell epitope NS5B2841-2849 (ARMILMTHF) has been shown to be limited by viral fitness costs as well as broad T cell cross-recognition, suggesting a potential mechanism of protection by HLA-B27. Here, we studied the subdominant HLA-B27 restricted epitope NS5B2936-2944 (GRAAICGKY) in order to further define the mechanisms of pr...

  10. Determination of HLA-B27 Subtypes in Iranian Patients with Ankylosing Spondylitis

    Mohamad Hossein Nicknam

    2008-03-01

    Full Text Available The human leukocyte antigen-B27 is one of the class I molecules of the major histocompatibility complex which is strongly associated with ankylosing spondylitis (AS. The strength of the disease association with B27 varies markedly among racial and ethnic populations. It is an allele family, which constitutes about 31 subtypes, with a considerable geographic and ethnic difference in distribution. It is important to know whether certain subtypes show any preferential association with AS. Because there is no report regarding HLA-B27 subtypes in Iranian patients with AS, the factthe main there are rarelystudies (if any; purpose of the present study was to assess the frequency of subtypes of human leukocyte antigen (HLA-B27 in patients with ankylosing spondylitis in Iranian populationOne hundred and nineteen AS patients (82 HLA-B27 positive and 37 HLA-B27 negative were selected for this study. HLA-B27 positive patients were selected screened for B*27 subtyping were performed by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP for B*27 subtyping.. The results of present study revealed that onlythat only two subtypes were detected in Iranian patients, including: B*2705 (52 patients, 63.4% and B*2702 (30 patients, 36.6%. Our results showed a restricted number of HLA-B27 subtypes associated with AS in Iran and an elevated frequency of the B*2705 allele in these patients similar to other Euro-Caucasoid (Aryan groups in the world.

  11. Clinical Characteristics of Patients with Spondyloarthritides and HLA-B27 Positive Antigen

    Glasnović, Marija; Bošnjak, Ivica; Šram, Miroslav; Vranješ, Željko; Včev, Aleksandar; Dobrošević, Blaženka; Sinčić Petričević, Jasminka; Horvatić, Elizabeta; Orkić, Želimir; Tadžić, Refmir; Soldo, Anamarija; Šišljagić, Dina; Dinjar, Kristijan

    2011-01-01

    The aim of this study was to present our experiences in diagnosing spondyloarthritides (SpA), and to list the most common clinical features of HLA-B 27 positive patients.The study included 65 HLA-B 27 positive patients with confirmed diagnosis of ankylosing spondylitis(AS) and psoriatic arthritis (PsA) who were analyzed between 2009 and 2010 in Clinic of Internal Medicine in Osijek. The diagnosis of seronegative spondyloarthritides was based on the ASAS (Assessment in AS Working G...

  12. HLA-B27与强直性脊柱炎的相关性研究进展%Research progress in the relationship between HLA-B27 and ankylosing spondylitis

    方懿; 蒋宗滨

    2011-01-01

    Background Ankylosing Spondylitis (AS) is a common autoimmune joint disease, which mostly occurs to young men. Early diagnose of AS is difficult and the treatment is not satisfactory at present. Studies have been released that there is a strong relationship bewteen Human leucocyte antigen-B27 (HLA-B27). It is estimated that 90% AS patients were HLA-B27 positive, which was thought of vital importance for early diagnosis of AS. Objective This paper will review the relationship between AS and HLA -B27 which would provide the base on diagnosis and treatment of AS. Content This paper focuses on AS pathogenesis, pathology and clinical manifestations to summarize the relationship and diagnosis significance between HLA -B27 and AS. Trend The HLA-B27 antigen has a high correlation with AS, which can be used as an important clinical indicator for early diagnosis of AS. However it should be mentioned that any exaggeration of the role of HLA-B27 in the diagnosis of AS should be avoided, particular in HLA-B27 negative patients.%背景 强直性脊柱炎(ankylosing spondylitis,AS)是一种常见的自身免疫性关节病,好发于年轻男性,该疾病目前早期诊断较闲难,治疗效果不理想,以往研究表明HLA-B27与AS有很强的相关性,90%左右的AS患者HLA-B27呈阳性,但是仍有10%的患者HLA-B27呈阴性,值得临床进一步研究.目的 现对HLA-B27与AS之间的相关性作一综述,以求为AS的临床诊断和治疗提供帮助.内容 从AS的发病机制、病理学改变和临床表现入手,总结HLA-B27与AS的关系及其对AS诊断的意义.趋向 HLA-B27 抗原的榆测与AS有很高的相关性,可作为临床上早期诊断的重要指标之一,但不能夸大HLA-B27的诊断作用尤其是HLA-B27阴性的患者.

  13. 流式细胞术检测HLA-B27抗原的表达及意义

    吕程; 刘宇; 蒋洪昆

    2008-01-01

    目的 通过流式细胞术对外周血白细胞HLA-B27抗原的检测,了解腰背疼痛和/或关节疼痛患者HLA-B27抗原的分布情况,探讨其在风湿性疾病中的临床应用价值.方法 采用流式细胞仪检测腰背疼痛和/或关节疼痛患者372例HLA-B27抗原的表达.结果 327例患者中HLA-B27阳性163例,总阳性率为43.82%,其中男性259例,HLA-B27阳性137例,阳性率为52.90%.女性113例,HLA-B27阳性26例,阳性率为23.00%.HLA-B27阳性患者年龄分布以青少年为主,12~40岁HLA-B27阳性患者141例,阳性率为37.9%,41~78岁HLA-B27阳性患者22例,阳性率为5.99%.结论 HLA-B27阳性患者以青少年男性为主.HLA-B27检测对各种关节性疾病尤其是脊柱关节性疾病的早期诊断与鉴别诊断具有重要的临床意义.

  14. Clinical Value of HLA-B27 in Ankylosing Spondylitis%人白细胞抗原HLA-B27在强直性脊柱炎中的临床意义

    蒋娟; 熊小敏; 张卫云; 李薇

    2014-01-01

    目的:探讨人白细胞抗原HLA-B27在强直性脊柱炎(AS)中的临床意义,及联合检测HLA-B27、C反应蛋白(CRP)和红细胞沉降率(ESR)的意义.方法:对18例AS患者、24例腰背痛患者和21健康体检者的血液标本进行HLA-B27、CRP、ESR检测,并比较其HLA-B27阳性率.结果:与健康对照组比较,AS组的3项指标均高于对照组(P<0.05),且AS组HLA-B27阳性率均高于另外2组(P<0.05).结论:HLA-B27在强直性脊柱炎诊断中具有重要意义,与其具有高度疾病相关性,联合检测HLA-B27及CRP比联合检测HLA-B27及ESR更有利于疾病诊断.

  15. Association between polymorphism of the vitamin D metabolism gene CYP27B1 and HLA-B27-associated uveitis. Is a state of relative immunodeficiency pathogenic in HLA B27-positive uveitis?

    Gernot Steinwender

    Full Text Available OBJECTIVE: Polymorphisms of the vitamin D metabolism gene CYP27B1 showed associations with multiple autoimmune diseases. The aim of this study was to investigate a possible association between the rs703842 A>G polymorphism of the CYP27B1 gene and HLA-B27-associated uveitis. DESIGN: One hundred fifty-nine patients with HLA-B27-associated uveitis, 138 HLA-B27-negative controls and 100 HLA-B27-positive controls were recruited for this retrospective case-control study. Main outcome parameters were genotype distribution and allelic frequencies determined by polymerase chain reaction. RESULTS: Carriers of the rs703842G allele were found significantly more often in patients with HLA-B27-associated uveitis than in HLA-B27-positive controls (p = 0.03. Between patients and HLA-B27-negative controls no significant difference in the genotype distribution of the rs703842 A>G polymorphism was found (p = 0.97. CONCLUSIONS: Our data suggest that the rs703842 A>G polymorphism may play a role in HLA-B27-associated uveitis.

  16. Punctate palmoplantar keratoderma associated with morbus Bechterew and HLA B 27. A family study.

    Gamborg Nielsen, P

    1988-01-01

    Four patients in a family with punctate palmoplantar keratoderma (Buschke-Fischer) associated with Morbus Bechterew and HLA B 27 in 3 of the family members are reported. Without severe side effect, the proband was successfully treated with 50 mg etretinate per day for 6 weeks. PMID:2459882

  17. HLA-B27检测在AS诊断中的临床应用

    昝海波; 王波

    2005-01-01

    目的:评价HLA-B27检测在强直性脊柱炎(AS)诊断中的临床诊断价值.方法:对比分析28例HLA-B27阴性AS患者和56例病程相同的HLA-B27阳性AS患者(1:2配对)的临床表现及实验室检查结果.结果:B27(-)组与B27(+)组最明显的差异是前者以女性多见(P<0.01),平均发病年龄偏晚(P<0.05);病情活动性指标的改变包括血沉和C-反应蛋白的升高在B27(-)组明显少于B27(+)组(P均<0.01).结论:B27(-)AS患者病情相对较轻,预后较好;女性患者病情较轻,发展较慢,预后较好.HLA-B27对AS有一定早期诊断价值,并与血沉、X线片联合检测可提高诊断正确率.

  18. Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis.

    Appel, H; Kuon, W; Kuhne, M; P. Wu; Kuhlmann, S.; Kollnberger, S.; Thiel, A.; Bowness, P.; Sieper, J

    2004-01-01

    Reports of the use of HLA-B27/peptide tetrameric complexes to study peptide-specific CD8+ T cells in HLA-B27+-related diseases are rare. To establish HLA-B27 tetramers we first compared the function of HLA-B27 tetramers with HLA-A2 tetramers by using viral epitopes. HLA-B27 and HLA-A2 tetramers loaded with immunodominant peptides from Epstein–Barr virus were generated with comparable yields and both molecules detected antigen-specific CD8+ T cells. The application of HLA-B27 tetramers in HLA-...

  19. Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis.

    Appel, H; Kuon, W; Kuhne, M; P. Wu; Kuhlmann, S.; Kollnberger, S.; Thiel, A.; Bowness, P.; Sieper, J

    2004-01-01

    Reports of the use of HLA-B27/peptide tetrameric complexes to study peptide-specific CD8+ T cells in HLA-B27+-related diseases are rare. To establish HLA-B27 tetramers we first compared the function of HLA-B27 tetramers with HLA-A2 tetramers by using viral epitopes. HLA-B27 and HLA-A2 tetramers loaded with immunodominant peptides from Epstein-Barr virus were generated with comparable yields and both molecules detected antigen-specific CD8+ T cells. The application of HLA-B27 tetramers in HLA-...

  20. 流式细胞术检测HLA-B27及其临床意义%Detection of HLA-B27 by flow cytometry and it's clinical evaluation

    金明威; 陈哲; 陈颖

    2011-01-01

    Objective: To study the clinical evaluation of HLA -B27 detection by flow cytometry (FCM) for diagnosing ankylostomiasis.Methods: 41 patients with AS, 62 patients with lumbago and 112 normal people were analyzed by FCM.Results: HLA -B27 were positive in 38 (92.6% ); among 41 patients with AS, 6 (9.67% ) of 62 patients with lumbago and 2 ( 1.78% ) of 112 normal persons.Conclusions: The positive rate of HLA - B27 in patients with AS is obviously higher than that of other groups.The detection of HLA - B27 by FCM can play an important role in diagnosing AS.%目的 通过流式细胞术检测外周血白细胞HLA-B27的表达,并探讨其时强直性脊柱炎(AS)的诊断价值.方法 利用流式细胞仪(FCM)检测41例AS患者、62例背痛及腰腿痛患者及112例健康体检者的外周血HLA-B27表达.结果 41例AS患者中,HLA阳性38例(92.6%);62例背痛腰腿痛患者中,HLA-B27阳性6例(9.67%);112例健康人群中,HLA-B27阳性2例(1.78%).结论 AS患者HLA-B27阳性率明显增高,HLA-B27检测可视为临床支持AS诊断的重要依据.

  1. 流式细胞仪在 HLA-B27检测中的应用价值

    刘文超; 杨桂强

    2014-01-01

    目的:探讨流式细胞仪在诊断强直性脊柱炎 HLA-B27检测中的应用价值。方法应用流式细胞仪对86例强直性脊柱炎(AS)病人检测 HLA-B27,来判断流式细胞仪在检测 HLA-B27的临床相关性。结果流式细胞仪检测 HLA-B27的阳性率达到了90.7%,无假阳性及假阴性。结论流式细胞仪检测 HLA-B27是临床诊断强直性脊柱炎的重要辅助诊断方法。

  2. STUDY ON THE HEREDITY RELATIONSHIP BETWEEN ANKYLOSING SPONDYLITIS AND HLA-B27%强直性脊柱炎及HLA-B27的遗传倾向研究

    王小敏; 赵英; 蔡俊宏; 吴艳; 符生苗

    2009-01-01

    [目的]通过检测海南籍强直性脊柱炎(AS)及亲属的HLA-B27的表型、基因型及亚型的分布情况,了解海南籍HLA-B27和AS的遗传倾向及发病情况,指导临床治疗,预防AS的发病.[方法]HLA-B27表型检测采用血清学技术,HLA-B27基因型和基因分型检测均采用序列特异性引物聚合酶链式反应(PCR-SSR)技术.[结果]6例海南籍的AS患者及家族成员共86例中B27阳性者患AS的概率为36.7%,其中男女比例约为7.6:1;有AS相关症状者的概率为36.7%,男女比例为1:5.9.43个HLA-B27阳性家庭中一级亲属AS患病率为30.26%,HLA-B27阳性患AS的比率为47.92%,其中男性为68.97%,女性为15.79%,男女比例为1:4.4.无论是父亲还是母亲HLA-B27阳性,其子女HLA-B27的阳性率基本相近.AS患者中HLA-B27阳性者占100%,HLA-B27表型和基因型基本相符,HLA-B27基因分型结果均为HLA-B2704型.[结论]海南地区AS发病率和HLA-B27阳性率都较其他地区高,具有很强的家族遗传倾向,AS发病率男性较女性高发,有AS相关症状者女性高于男性.HLA-B27基因亚型为HLA-B2704.

  3. HLA-B27检测在强直性脊柱炎诊断中的临床价值%The clinical value of HLA-B27 in the diagnosis of ankylosing spondyfitis

    张虹; 顾猛

    2009-01-01

    目的 探讨HLA-B27抗原检测在强直性脊柱炎(AS)早期诊断中的临床价值.方法 使用ELISA法对450例健康体检者(非AS对照组)、462例AS疑似患者(AS疑似组)和80名AS患者(AS组)进行HLA-B27抗原检测.结果 非AS对照组、AS疑似组和AS组的HLA-B27阳性率分别为3.3%、48.9%和92.5%,AS组、AS疑似组的HLA-B27阳性率明显高于非AS对照组(P<0.01),AS组的HLA-B27阳性率明显高于AS疑似组(P<0.01).结论 HLA-B27抗原与AS疾病相关,检测HLA-B27抗原对疑似AS患者的早期诊断有重要意义.

  4. 强直性脊柱炎867例HLA-B27的表达及意义%Clinical significance of HLA-B27 expression in 867 patients with ankylosing spondylitis

    倪吴花; 胡晓霞; 章圣辉; 吴春雷; 吴建波

    2008-01-01

    目的:通过检测临床疑为强直性脊柱炎(AS)患者的HLA-B27表达,探讨HLA-B27抗原的检测在AS早期诊断中的意义.方法:采用流式细胞术对1 807例疑为AS患者外周血进行HLA-B27表达的检测.结果:在867例诊断为AS的患者中,HLA-B27阳性758 例,HLA-B27检测AS的敏感性为87.4%(758/867),特异性为91.9%(864/940).诊断正确率为89.8%结论:AS与HLA-B27阳性高度相关,临床疑为AS的患者若加上流式HLA-B27抗原检测结果将对AS的早期诊断起到重要作用.

  5. 强直性脊柱炎检测HLA-B27、ASO、RF、CRP的临床意义%The Clinical Significance of Testing HLA- B27、ASO、RF、CRP in Ankylosing Spondylitis

    范洪; 郑小丽; 侯英荣; 冯秀河

    2004-01-01

    目的探讨HLA-B27、ASO、RF、CRP检测在强直性脊柱炎(AS)诊断与鉴别诊断中的意义.方法抽取EDTA(K2)抗凝血2ml,采用磁珠酵素免疫法检测HLA-B27,采用胶乳凝集法检测ASO、RF、CRP.结果31例正常健康者HLA-B27、ASO、RF、CBP检测结果均为阴性.108例疑似AS患者中,HLA-B27阳性率为30.6%(33/108).33例HLA-B27阳性患者中,ASO阳性率为6.1%(2/33),RF阳性率为3.0%(1/33),CRP阳性率为12.1%(4/33).结论 HLA-B27的检测可明确AS诊断,特别是在不典型AS诊断中具有重要的临床价值.ASO、RF检测可用于AS的鉴别诊断.疑似AS患者HLA-B27阳性者中,其活动期的CBP比率较低.

  6. Molecular mechanism of the susceptibility difference between HLA-B*27:02/04/05 and HLA-B*27:06/09 to ankylosing spondylitis: substitution analysis, MD simulation, QSAR modelling, and in vitro assay.

    Cheng, X; Mei, Y; Ji, X; Xue, Q; Chen, D

    2016-05-01

    The human leukocyte antigen HLA-B27 is directly involved in the disease pathogenesis of ankylosing spondylitis (AS). HLA-B27 has a high degree of genetic polymorphism, with 105 currently known subtypes; the presence of aspartic acid at residue 116 (Asp116) has been found to play an essential role in AS susceptibility. Here, we systematically investigated the molecular mechanism of the susceptibility difference between the AS-associated subtypes HLA-B*27:02/04/05 and AS-unassociated subtypes HLA-B*27:06/09 to AS at sequence, structure, energetic and dynamic levels. In total seven variable residues were identified among the five studied HLA-B27 subtypes, in which Asp116 can be largely stabilized by a spatially vicinal, positively charged His114 through a salt bridge, while five other variable residues seem to have only a marginal effect on AS susceptibility. We also employed a quantitative structure-activity relationship approach to model the statistical correlation between peptide structure and affinity to HLA-B*27:05, a genetic ancestor of all other HLA-B27 subtypes and associated strongly with AS. The built regression predictor was verified rigorously through both internal cross-validation and external blind validation, and was then employed to identify potential HLA-B*27:05 binders from >20,000 cartilage-derived self-peptides. Subsequently, the binding potency of the top five antigenic peptides to HLA-B*27:05 was assayed in vitro using a FACS-based MHC stabilization experiment. Consequently, two (QRVGSDEFK and LRGAGTNEK) out of the five peptides were determined to have high affinity (BL50 = 5.5 and 15.8 nM, respectively) and, as expected, both of them possess positively charged Lys at the C-terminus. PMID:27228481

  7. HLA-B27阳性与阴性未分化脊柱关节病的临床比较%Comparison of undifferentiated spondyloarthropathy patients with positive or negetive HLA-B27

    杨积保; 张慧群; 刘智; 李志军

    2010-01-01

    目的:探讨血清人类白细胞抗原-B27(HLA-B27)阳性与阴性未分化脊柱关节病(undifferentiated spondyloarthropathy,uSpA)患者临床表现及预后的差异,为临床诊疗提供借鉴.方法:根据血清HLA-B27是否阳性将120例uSpA患者分为两组,阳性组78例,阴性组42例.分析HLA-B27阳性组与阴性组的临床表现及相关实验室检查结果,比较两组间的差异;并对部分患者进行3年以上随访观察,了解其病情变化.结果:HLA-B27阳性组患者发病年龄显著早于HLA-B27阴性组(P<0.05);发热、消瘦、疲倦等全身症状表现HLA-B27阳性组显著多于HLA-B27阴性组,且较严重(P<0.05);实验室检查中血沉以HLA-B27阳性组显著为高(P<0.05);骶髂关节X线表现亦以HLA-B27阳性组显著为高(P<0.05).而两组性别及外周关节炎等表现差异无统计学意义(P>0.05).随访发现HLA-B27阳性组3年后发展为强直性脊柱炎者显著多于HLA-B27阴性组(P<0.05).结论:HLA-B27阳性组uSpA患者发病年龄较早,临床症状较重,更有可能发展为强直性脊柱炎.

  8. Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter's syndrome. Molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease

    1987-01-01

    Ankylosing spondylitis (AS) and Reiter's syndrome (RS) both show a strong correlation with the HLA B27 haplotype. We studied whether sharing of homologous amino acid sequences in the HLA B27 antigen with an invading microbe might occur, and if so, what is the biological significance of such homology. In a computer search of the Dayhoff data bank, we found a homology of six consecutive amino acids between HLA B27.1 antigen residues 72-77 and Klebsiella pneumoniae nitrogenase residues 188-193. ...

  9. 强直性脊柱炎与HLA-B27相关性的研究进展%Recent advancement about dependability of ankylosing spondylitis and HLA-B27

    孙翠华; 孟凡杰; 王玉芳; 王健

    2007-01-01

    强直性脊柱炎是一种发病率较高的慢性进展性风湿疾病,与人类白细胞抗原-B27(HLA-B27)密切相关,本文总结了近几年对HLA-B27各方面的研究成果及最新进展,有助于了解HLA-B27在此疾病中的确切作用,并可以辅助临床医师对强直性脊柱炎进行诊治.

  10. Association of HLA-B27 and ERAP1 with ankylosing spondylitis susceptibility in Beijing Han Chinese.

    Zhang, Z; Dai, D; Yu, K; Yuan, F; Jin, J; Ding, L; Hao, Y; Liang, F; Liu, N; Zhao, X; Long, J; Xi, Y; Sun, Y-Y

    2014-05-01

    This study investigated the genetic polymorphisms of HLA-B27, together with polymorphisms on endoplasmic reticulum aminopeptidase 1 (ERAP1), and susceptibility for ankylosing spondylitis (AS) in the Beijing Han population. A case-control study was carried out for 602 AS patient samples and 619 matched controls of Han Chinese. HLA-B27 genotyping was performed by polymerase chain reaction-sequence specific primers (PCR-SSP), and four ERAP1 SNPs (rs27037, rs27980, rs27582, and rs27434) were selected and genotyped on the Sequenom iPlex platform (Sequenom, San Diego, CA). Association analysis was performed using the likelihood ratio χ(2) test. This study identified four HLA-B27 alleles in Beijing Han AS patients, B*27:02, B*27:04, B*27:05, and B*27:07, of which B*27:05 was the most significant geographical different subtype among AS patients in Chinese. Our results confirmed that HLA-B27 was strongly associated with AS (P=1.9 × 10(-150) ), and the most strongly associated alleles were B*27:04, B*27:05, and B*27:02. Our study also confirmed a weak association between ERAP1 (rs27434) and AS. We also observed that for HLA-B*27:02 and HLA-B*27:04 positive AS patients, rs27434 and rs27582 were associated with AS. In contrast, for HLA-B27-negative and HLA-B*27:05-positive AS patients, this association was not observed. This is the first study to show that both B27 and ERAP1 are AS genetic susceptibility genes in Beijing Han. Interactions between ERAP1 and HLA-B*27:02 and B*27:04 may play an important role in the AS pathogenesis. PMID:24666027

  11. IgG and IgA immune response against klebsiella in HLA-B27-associated anterior uveitis.

    Kijlstra, A.; Luyendijk, L; van der Gaag, R; van Kregten, E; Linssen, A; Willers, J M

    1986-01-01

    Enteric infections with Gram-negative bacteria are thought to play an important part in HLA-B27-associated disease such as Reiter's syndrome and reactive arthritis. But the role of bacterial infections in HLA-B27-positive ankylosing spondylitis (AS) and acute anterior uveitis (AU) is still controversial. A special interest has recently been devoted to the role of klebsiella infection in HLA-B27-associated disease. We studied the humoral immune response against a 'cross-reactive' strain of Kle...

  12. Povezanost mikrosatelita HLA i gena HLA-B*27 u bolesnika s psorijatičnim artritisom u hrvatskoj populaciji

    Štimac, Davor; Grubić, Zorana; Štingl, Katarina; Perić, Porin; Ćurković, Božidar; Žunec, Renata

    2011-01-01

    Istraživana je raznovrsnost četiri mikrosatelita HLA (D6S248, D6S2674, D6S2811 i D6S273) u skupini bolesnika s psorijatičnim artritisom (PsA) (N=22) i zdravim osobama (K; N=94) pozitivnima za gen HLA-B*27, te povezanost haplotipskih veza gena HLA-B*27 s PsA. Svi ispitanici bili su prethodno tipizirani za gene HLA-A i -B metodom PCR-SSP i bili su HLA-B*27 pozitivni. Mikrosateliti HLA su analizirani metodom PCR-STR i elektroforezom u ALFexpress sekvenceru. Analiza raspodjele alela mikrosatelita...

  13. Yersinia enterocolitica serotype O:3 alters the expression of serologic HLA-B27 epitopes on human monocytes.

    Wuorela, M; Jalkanen, S; Kirveskari, J; Laitio, P; Granfors, K

    1997-01-01

    The expression of serologic HLA-B27 epitopes on leukocytes of patients with reactive arthritis or ankylosing spondylitis has been shown to be modified in the course of the disease. The purpose of this work was to study whether phagocytosis of arthritis-triggering microbes in vitro alters the expression of HLA-B27 molecules on human antigen-presenting cells and to characterize the underlying mechanisms. Human monocytes and HLA-B27- or HLA-A2-transfected human U-937 cells were exposed to Yersin...

  14. Arthrite rhumatoïde juvénile et HLA-B27.

    Mathon, G; ParÉ, C.; Ménard, H; Tétreault, L; Camerlain, M

    1980-01-01

    Forty children with juvenile rheumatoid arthritis were studied to determine the frequency of the histocompatibility antigen HLA [human leukocyte antigen)-B27 in this disease and to characterize the arthropathy associated with this antigen. HLA-B27 was detected in four patients (10%). Its presence was associated in a statistically significant manner with sacroiliitis demonstrated radiologically and with a greater age at the time symptoms in the joints first appeared; this age was, on average, ...

  15. HLA-B27 Expression Does Not Modulate Intracellular Chlamydia trachomatis Infection of Cell Lines

    Young, J. L.; Smith, L; Matyszak, M. K.; Gaston, J S H

    2001-01-01

    Chlamydia trachomatis is an obligate intracellular pathogen. Infection of susceptible individuals with this bacterium can trigger the development of reactive arthritis, an acute inflammation that is associated with the expression of the class I major histocompatibility antigen, HLA-B27. Other facultative intracellular pathogens, such as Yersinia and Salmonella spp., are also known triggers of reactive arthritis. Previous studies report conflicting results concerning whether the presence of HL...

  16. Antinuclear antibody and HLA-B27 positive uveitis: combination of two diseases ?

    Bosch-Driessen, E.H.; Lardy, N.M.; Rothova, A

    1997-01-01

    AIMS/BACKGROUND—Anterior uveitis associated with juvenile chronic arthritis concerns two different clinical entities: firstly, antinuclear antibody (ANA) positive patients who have a chronic anterior uveitis with severe complications and often a poor visual prognosis; secondly, usually HLA-B27 positive children, predominantly boys, with unilateral recurrent anterior uveitis. Three patients are described who had a combination of clinical and laboratory features of both diseases.
METHODS—Retros...

  17. HLA-B27 positive juvenile arthritis with cardiac involvement preceding sacroiliac joint changes

    Lee, S; Im H, Y; Schueller, W

    2001-01-01

    While cardiovascular disease develops in up to 50% of adult patients with ankylosing spondylitis, it is very uncommon in its juvenile counterpart. Regarding the early stage of the disease, before onset of sacroiliac joint changes, only two cases with aortic incompetence have been published while reports of mitral valve involvement are not available. A 13 year old boy is described with an HLA-B27 positive asymmetric oligoarthritis and enthesitis, without back pain or radiographic evidence of s...

  18. Association of HLA-B27 status and gender with sacroiliitis in patients with ankylosing spondylitis

    Xiong, Jiangbiao; Chen, Jing; Tu, Jianxin; Ye, Wenjing; Zhang, Zhiyong; Liu, Qiaoqiong; Zhu, Xiaochun

    2014-01-01

    Objective: To observe the influence of human leucocyte antigen B27 (HLA-B27) status and gender on sacroiliitis on computed tomography (CT) in ankylosingspondylitis (AS). Methods: We reviewed the archived medical records of the AS inpatients admitted in the Rheumatology Department of the First Affiliated Hospital of Wenzhou Medical University during the period from January 2007 through January 2013 and finally 386 patients were included in the study. The severity of sacroiliitis on CT was eval...

  19. The role of HLA-B27 molecules in the pathogenesis of ankylosing spondylitis

    R. Pala

    2011-09-01

    Full Text Available Ankylosing Spondylitis (AS is characterised by the strongest association with an HLA antigen ever described for any disease. It represents therefore the ideal model for the understanding of the link between immune-mediated diseases and the HLA system. The role of HLA-B27 in the pathogenesis of AS will be discussed focusing on the recently described higher expression of these molecules in patients with AS compared with healthy controls.

  20. Functional variants of ERAP1 gene are associated with HLA-B27 positive spondyloarthritis.

    Cherciu, M; Popa, L O; Bojinca, M; Dutescu, M I; Bojinca, V; Bara, C; Popa, O M

    2013-09-01

    We investigated two nonsynonymous variants (rs30187 and rs27044) of ERAP1 gene in HLA-B27 positive individuals (150 spondyloarthritis and 108 controls) and in general ankylosing spondylitis (AS) patients (n = 137) vs random controls (n = 139). Both single nucleotide polymorphisms (SNPs) were associated with the risk of spondyloarthritis [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.24-2.62, P = 0.001 for rs30187, OR 1.58, 95% CI 1.07-2.34, P = 0.02 for rs27044]. The CC haplotype was a protective factor (P = 0.002), while the TG haplotype was a risk factor (P = 0.01) for spondyloarthritis. The SNP rs30187 was also associated with the risk of HLA-B27+ AS. For the general group of AS, the carriers of minor alleles showed an increased risk for the disease (OR 1.92, 95% CI 1.17-3.13 for rs30187, OR 1.74, 95% CI 1.08-2.80 for rs27044). This is the first study that shows the association of ERAP1 gene variants and haplotypes with HLA-B27 positive spondyloarthritis. PMID:23800305

  1. Allicin Attenuates Inflammation and Suppresses HLA-B27 Protein Expression in Ankylosing Spondylitis Mice

    Xin Gu

    2013-01-01

    Full Text Available Here we aimed to determine the therapeutic effect of allicin on ankylosing spondylitis (AS and explore the mechanism(s of action. AS mouse model was constructed by transferring the HLA-B2704 gene into Kunming mice and verified by RT-PCR and CT imaging. Verified AS mice were randomly divided into model group ( and allicin-treated groups (50, 100, and 200 mg/kg, resp., , p.o., for 2 months. Wild type mice were used as control (. The levels of AS-related inflammatory factors were measured by ELISA. mRNA and protein expressions of HLA-B27 were checked by RT-PCR and western blotting. As the results, the mouse model of AS was successfully established, and high-dose allicin could markedly alleviate spine inflammatory injury possibly via reducing the secretion of the inflammatory factors (IL-6, IL-8, and TNF-α sharply in AS mice. Moreover, allicin significantly inhibited HLA-B27 protein translation but failed to suppress HLA-B27 gene transcription in AS mice, indicating a posttranscriptional mechanism of this modulation. In conclusion, allicin has potential to be used for AS treatment as an anti-inflammatory nutraceutical.

  2. The impact of the strength of HLA-B27 positive on seronegtive spondyloarthropathies%HLA-B27阳性的强弱对血清阴性脊柱关节病的影响评估

    陈睿; 宋恒平; 倪凤民; 邵先安; 张皓

    2013-01-01

    目的 探讨HLA-B27的阳性强弱对血清阴性脊柱关节病(SPA)诸病种的诊治影响评估.方法 78 例SPA(血清阴性脊柱关节病)中AS(强直性脊柱炎)32 例,USPA(未分化脊柱关节病)42 例,PSA 3例,ReA1 例,计HLA-B27强阳性4 例,阳性30 例,弱阳性40 例,阴性4 例.结果 随访2耀20年,1例HLA-B27强阳性AS 患者不遵医嘱治疗,6 年后两髋关节损害致残,其他3 例HLA-B27强阳性患者急性发作多次,但病情控制较好,30 例HLA-B27阳性患者中3 例失访,其他按正规抗AS 治疗,病情平稳其中男性28例.40 例HLA-B27弱阳性患者中有2 例在1耀4 年后被确诊为AS,1例被诊断反应性关节炎,且女性有29 例,其他病情平稳,HLA-B27阴性4 例,行抗AS 治疗,骶髂关节炎在玉耀域级之间未进一步发展.结论 HLA-B27强阳性及阳性SPA 多见于男性,病情发展快,难以控制病情,HLA-B27强阳性SPA患者致残率高,HLA-B27弱阳性的SPA、USPA患者多见于女性,症状一般较轻,易于控制.HLA-B27阴性SPA 患者更较少见,病情发展慢,且易于控制发展.

  3. Bilateral macular thickening in mild unilateral anterior uveitis: is HLA-B27 involved?

    Wexler Alexandra

    2012-07-01

    Full Text Available Abstract Background Macular thickening (MT without clinically recognized macular edema has been described in anterior uveitis (AU. Although fellow-eyes of patients have been used as controls in several studies, little is known about macular thickness in these eyes. We studied the rate and extent of MT in both AU-affected and quiescent fellow-eyes of phakic AU patients with good visual acuity (VA. We also assessed macular thickness related to HLA-B27 presence and to recurrence, since these issues have been almost unexplored by previous optical coherence tomography (OCT studies. Methods Patients with AU were prospectively included and macular thickness was measured with OCT initially and on follow up. Macular thickness in patients’ affected eyes (n = 30 as well as in their quiet fellow-eyes (n = 28 was compared with eyes of age- and gender matched controls. Inter-ocular differences in macular thickness between AU affected eyes and their fellow-eyes were assessed in patients (n = 28, also in a subgroup with visual acuity ≥ 0.8 (n = 23 by one-sample Student’s t-tests. Inter-ocular differences were also assessed related to HLA-B27 presence and related to the status of current AU episode (initial or relapse. Results Subclinical MT is present in both quiet fellow-eyes and AU-affected eyes of patients. MT was found in most cases of AU, even in phakic eyes with good VA. There was a larger increase in macular thickness in HLA-B27-positive than in HLA-B27-negative patients. No differences in macular thickness were found between patients with their first AU episode and patients with recurrent episodes. Conclusions MT probably reflects systemic immune-mediated response to the inflammatory disorder in AU, and it is possible that HLA-B27-related factors are involved in the pathogenesis of AU. These observations are in line with and extend the current understanding of the mechanisms behind MT in AU.

  4. VALUE OF FLOW CYTOMETRY DETECTION OF HLA-B27 ANTIGEN IN THE DIAGNOSIS OF AS%流式细胞术检测HLA-B27抗原在AS诊断中的价值

    邱金英

    2009-01-01

    目的 探讨人类白细胞抗原-B27(HLA-B27)检测对强直性脊柱炎(AS)在临床诊断中的价值.方法 应用流式细胞术对567例门诊及住院疑似AS患者外周血进行HLA-B27表达的检测.结果 567例中,HLA-B27阳性检出率为43.39%(246/567).按照纽约标准诊断为AS的252例患者中,HLA-B27阳性率为91.67%(231/252).HLA-B27检测对诊断AS的敏感度为91.67%(221/252),特异度为95.24%(300/315),诊断正确率为93.65%(531/567).结论 HLA-B27和AS有很强的相关性,使用流式细胞术进行检测是较好的方法.

  5. Structural analysis of an HLA-B27 functional variant: identification of residues that contribute to the specificity of recognition by cytolytic T lymphocytes.

    Vega, M A; Ezquerra, A.; S Rojo; Aparicio, P.; Bragado, R; López de Castro, J. A.

    1985-01-01

    The structure of a variant HLA-B27 antigen, B27.2, that is distinguished from the HLA-B27.1 and HLA-B27.3 subgroups by specific cytolytic T lymphocytes has been established by comparative peptide mapping and sequence analysis. There are only three amino acid substitutions between B27.1 and B27.2: aspartate-77, threonine-80, and leucine-81 in HLA-B27.1 are changed to asparagine-77, isoleucine-80, and alanine-81 in HLA-B27.2. These changes account for their single charge difference detectable b...

  6. A comparison of self-reported joint symptoms following infection with different enteric pathogens: effect of HLA-B27

    Schiellerup, P.; Krogfelt, K.A.; Locht, H.

    2008-01-01

    OBJECTIVE: We conducted a case-case comparison study to estimate the attack-rate of reactive joint pain (JPrea) following intestinal infections, and evaluated whether the susceptibility and severity of joint symptoms was associated with the tissue-type HLA-B27. METHODS: Consecutive patients with.......8%); Yersinia, 21 (23.1%); Shigella, 10 (9.8%); and E. coli, 28 (9.7%). There was a significant association between severity of gastroenteritis and development of arthralgia (p = 0.001). The odds ratio (OR) for JPrea in an HLA-B27-positive individual was 2.62 (95% CI 1.67-3.93) for the entire group. A...... significant association between JPrea and HLA-B27 was found for Salmonella, Shigella, and Yersinia; not, however, for Campylobacter and E. coli. HLA-B27-positive patients had a significantly increased risk for severe joint symptoms. CONCLUSION: Our study shows that JPrea after GI infection is positively...

  7. Ultrasonographic assessment of enthesitis in HLA-B27 positive patients with rheumatoid arthritis, a matched case-only study.

    Antonio Mera-Varela

    Full Text Available INTRODUCTION: HLA-B27 has a modifier effect on the phenotype of multiple diseases, both associated and non-associated with it. Among these effects, an increased frequency of clinical enthesitis in patients with Rheumatoid Arthritis (RA has been reported but never explored again. We aimed to replicate this study with a sensitive and quantitative assessment of enthesitis by using standardized ultrasonography (US. METHODS: The Madrid Sonography Enthesitis Index (MASEI was applied to the US assessment of 41 HLA-B27 positive and 41 matched HLA-B27 negative patients with longstanding RA. Clinical characteristics including explorations aimed to evaluate spondyloarthrtitis and laboratory tests were also done. RESULTS: A significant degree of abnormalities in the entheses of the patients with RA were found, but the MASEI values, and each of its components including the Doppler signal, were similar in HLA-B27 positive and negative patients. An increase of the MASEI scores with age was identified. Differences in two clinical features were found: a lower prevalence of rheumatoid factor and a more common story of low back pain in the HLA-B27 positive patients than in the negative. The latter was accompanied by radiographic sacroiliitis in two HLA-B27 positive patients. No other differences were detected. CONCLUSION: We have found that HLA-B27 positive patients with RA do not have more enthesitis as assessed with US than the patients lacking this HLA allele. However, HLA-B27 could be shaping the RA phenotype towards RF seronegativity and axial involvement.

  8. Aetiology and pathogenesis of reactive arthritis: role of non-antigen-presenting effects of HLA-B27

    Vähämiko, Sanna; Penttinen, Markus A.; Granfors, Kaisa

    2005-01-01

    Spondyloarthropathies are inflammatory diseases closely associated with human leukocyte antigen (HLA)-B27 by unknown mechanisms. One of these diseases is reactive arthritis (ReA), which is typically triggered by Gram-negative bacteria, which have lipopolysaccharide as an integral component of their outer membrane. Several findings in vivo and in vitro obtained from patients with ReA and from different model systems suggest that HLA-B27 modulates the interaction between ReA-triggering bacteria...

  9. HLA-B27 modulates the survival of Salmonella enteritidis in transfected L cells, possibly by impaired nitric oxide production.

    Virtala, M; Kirveskari, J; Granfors, K

    1997-01-01

    Reactive arthritis is triggered by certain microbes that cause primary infections mainly on the gastrointestinal or urogenital mucosa. The disease is strongly associated with HLA-B27. Long persistence of causative microbes or their structures in the body has been thought to have an important role in the pathogenesis of reactive arthritis. This suggests that the elimination of the microbes causing reactive arthritis is ineffective or disturbed in HLA-B27-positive individuals developing this co...

  10. 流式细胞仪检测HLA-B27及其临床意义

    徐建

    2014-01-01

    目的:通过流式细胞术对人体外周血HLA-B27的检测,来评价HLA-B27辅助临床诊断强直性脊柱炎(AS)的应用价值。方法56例强直性脊柱炎患者和51例健康体检者,用荧光标记的抗HLA-B27/CD3单克隆抗体与其外周血(以EDTA-K2抗凝)特异性结合,用流式细胞仪检测其荧光强度来反映细胞表面 HLA-B27抗原的表达。结果从流式细胞术检测显示,56例AS患者中,HLA-B27阳性51例,阳性率为91.1%;51例健康体检者中,HLA-B27阳性3例,阳性率为5.9%。两者存在显著性差异,P<0.01。结论 AS患者HLA-B27阳性率明显高于正常人,所以检测HLA-B27对强直性脊柱炎的诊断与鉴别诊断有着重要的意义。

  11. 湖南地区汉族健康人群HLA-B*27基因多态性调查

    谢毓滨; 张钢; 曹丽群; 李涛

    2012-01-01

    目的 调查湖南地区汉族健康人群中HLA-B* 27基因多态性.方法 对3488名湖南汉族健康造血干细胞志愿捐献者进行HLA -B基因测序分型,对HLA-B* 27健康携带者亚型分布情况进行分析.结果 3488名湖南汉族志愿捐献者中,共检出HLA-B*27基因健康携带者99名,在人群中的分布比例为2.84%,男女比例无明显差异.99名健康携带者中,共检出HLA-B*27基因亚型6种,其中以HLA -B*27∶04为主(68/100),其次是HLA-B* 27∶05(18/100),HLA -B*27∶06(7/100),HLA-B* 27∶ 07(3/100),HLA-B* 27∶ 02 (2/100),HLA-B*27:24(2/100).结论 湖南地区汉族健康人群HLA-B* 27基因亚型以B*27∶04、B*27∶05为主.

  12. 强直性脊椎炎患者HLA-B27的检测意义

    张颖新; 王凤菊; 颜敏

    2003-01-01

    目的探讨强直性脊椎炎(AS)患者HLA-B27的检测意义.方法 2002年3月至2002年9月,因关节病前来诊断的患者276例,用单抗板淋巴细胞毒法测其白细胞上的HLA-B27抗原.结果确诊为AS的患者中HLA-B27阳性率96.3%(119/124)显著高于非AS的病人的HLA-B27阳性率2.2%(3/152)(P<0.001),B27阴性AS患者发病年龄高于B27阳性患者,且男性多于女性,男女发病年龄相比无统计学意义.结论 HLA-B27与强直性脊椎炎有很强的关联性,对于长期不明原因的腰腿痛患者结合临床及X线HLA-B27可作为AS的早期诊断和鉴别诊断指标.

  13. HLA-B27检测在强直性脊柱炎中的临床应用

    蒋叙川; 卢峰

    2012-01-01

    目的:探讨HLA-B27抗原检测在强直性脊柱炎(AS)早期诊断中的临床价值.方法:使用流式细胞技术对30例健康体检者、41例AS疑似患者和52名AS患者进行HLA-B27抗原检测.结果:体检对照组、AS疑似组和AS组的HLA-B27阳性率分别为0%、12.2%和90.4%,AS组、AS疑似组的HLA-B27阳性率明显高于体检对照组(P<0.01),AS组的HLA-B27阳性率明显高于AS疑似组(P<0.01).结论:HLA-B27抗原与AS疾病相关,检测HLA-B27抗原对疑似AS患者的早期诊断有重要意义.

  14. HLA-B27 frequency in a group of patients with psoriatic arthritis Freqüência de HLA-B27 em uma amostra de pacientes com artrite psoriática

    Danilo Garcia Ruiz

    2012-12-01

    Full Text Available BACKGROUND: HLA-B27 is associated with spondyloarthritis, a group of diseases that includes psoriatic arthritis. OBJECTIVES: To describe the HLA-B27 frequency in a group of Brazilian patients with psoriatic arthritis and correlate its presence or absence with their clinical manifestations. METHODS: Cross-sectional study with 44 psoriatic arthritis patients of a Rheumatology clinic. Demographic and social data were recorded, as were skin and joints clinical examination. HLA-B27 was tested. All data were processed descriptively and comparatively by appropriate software. Parametric and non parametric tests were used with 5% statistical significance. RESULTS: HLA-B27 was negative in 32 of the 44 patients (72,7%. Most of them were male, Caucasian, living in Rio de Janeiro, with plaque type psoriasis and average age of 52,9 years. There was statistical significant correlation between positive HLA-B27 and male gender (p=0,004. Negative HLA-B27 had a tendency to correlate with hands and wrists arthritis (p=0,07. There was an inverse significant correlation between HLA values and Schöber's test (p=0,02. CONCLUSION: Although HLA-B27 is negative in most of patients, it is significantly associated to male gender and inversely correlated with Schöber's test.FUNDAMENTOS: O HLA-B27 está associado às espondiloartrites, grupo de doenças que engloba, entre outras, a artrite psoriásica. OBJETIVOS: Descrever a freqüência de HLA-B27 em uma amostra de pacientes brasileiros com artrite psoriásica e correlacionar sua presença ou ausência com as manifestações clínicas dos mesmos. MÉTODOS: Estudo transversal avaliando 44 pacientes com artrite psoriásica de um ambulatório de Reumatologia. A avaliação consistia em registro de informações demográficas e sociais, exame clínico da pele e das articulações e pesquisa de HLA-B27. Os dados gerados foram tratados por meio de estatística descritiva e comparativa em Software apropriado. Foram utilizados

  15. Detection and clinical significance of HLA- B27 antigen by flow cytometry%流式细胞术检测HLA-B27抗原的表达及临床意义

    陆春伟; 佟海侠

    2010-01-01

    目的 评价流式细胞仪法检测HLA-B27抗原对强直性脊柱炎(AS)、急性前葡萄膜炎(AAU)的临床诊断价值.方法 用流式细胞仪检测85例AS患者、40例AAU患者、90例背痛和腰腿痛患者以及80例健康对照组的HLA-B27抗原表达.结果 AS组HLA-B27检测阳性率(91.8%)高于背及腰腿痛组(5.6%)和健康体检组(3.8%);AAU组HLA-B27检测阳性率(52.5%)高于健康体检组;背及腰腿痛组HLA-B27检测阳性率与健康对照组比较无意义.结论 流式细胞仪法检测HLA-B27抗原对AS的临床诊断有较高敏感度和特异度,是一种准确、有效的实验诊断方法;对AAU患者进行HLA-B27检测,对评价其临床特征和预后有一定价值.

  16. Phosphorylation of STAT-1 serine 727 is prolonged in HLA-B27-expressing human monocytic cells.

    Marja Ruuska

    Full Text Available A tissue antigen, HLA-B27, is strongly associated with a group of rheumatic diseases called spondyloarthritides. Despite the intensive research, the exact role of HLA-B27 in the pathogenesis of these diseases is still unclear. Here we studied whether HLA-B27 modulates the phosphorylation of signal transducer and activator of transcription 1 (STAT-1 serine 727 residue and the localization of STAT-1 in Salmonella-infected human monocytic cells. In addition, we studied the role of signaling molecule double-stranded RNA activated protein kinase (PKR in these modulatory effects. U937 human monocytic cell transfectants stably expressing wild type HLA-B27 or mutated HLA-B27 heavy chains with amino acid substitutions in the B pocket were prepared. The PMA-differentiated cells were infected with S. enteritidis. Western blotting was used to detect the phosphorylation of STAT-1, and to visualize the localization of STAT-1 in the cells confocal microscopy was used. Specific inhibitors were employed to study the role of PKR in STAT-1 phosphorylation. We discovered that the phosphorylation of STAT-1 serine 727 is prolonged in cells expressing misfolding forms of HLA-B27 after S. enteritidis infection, whereas in mock cells and in cells expressing mutated, non-misfolding HLA-B27 the phosphorylation of serine 727 is transient. Interestingly, STAT-1 serine 727 phosphorylation is partly dependent on PKR. In addition, more STAT-1 is localized in the nucleus of HLA-B27-expressing cells, even before an external trigger, when compared to mock cells. In conclusion, our results show that the phosphorylation of STAT-1 serine 727 residue is prolonged in HLA-B27-expressing monocyte-macrophage U937 cells after bacterial infection. This is of interest since the phosphorylation of serine 727 on STAT-1 is suggested to contribute to macrophage activation and promote inflammatory responses. Therefore, our results provide a mechanism which explains how the expression of an HLA-B

  17. HLA-B27 associated reactive spondyloarthropathies in a Dutch military hospital.

    Lionarons, R J; van Zoeren, M; Verhagen, J N; Lammers, H A

    1986-01-01

    Forty-two male patients with reactive spondyloarthropathies in a Dutch military hospital are described with mean age of onset 21.9 years. Peripheral arthritis or sacroiliitis was present in all, eye symptoms in 21 (50%), and genitourinary disease in 15 (35.7%). Evidence of antecedent sexually acquired or enterocolitic infection was found only in three (7.2%). HLA-B27 antigen was detected in 34 (81%) of 42 patients. Additional data suggest that reactive spondyloarthropathies are the most commo...

  18. Observer variation in grading sacroiliac radiographs in HLA-B27 positive individuals

    Hollingsworth, P.N.; Cheah, P.S.; Dawkins, R.L.; Owen, E.T.; Calin, A.; Wood, P.H.N. (Royal Perth Hospital (Australia))

    1983-04-01

    This study attempts to reconcile the apparent differences in the reported frequency of ankylosing spondylitis and radiological sacroilitis in HLA-B27 positive individuals. Pelvic radiographs from 125 Busselton subjects were mixed with 81 other films selected to illustrate the possible range of sacroiliac changes and were graded by observers who were involved in 2 of the conflicting studies and by a 3rd independent observer. Concordance was high for advanced bilateral disease but not for unilateral and milder changes. Variation between observers and the interpretation of sacroiliac radiographs is sufficiently large to account for much of the disagreement between frequency estimates.

  19. HLA-B27在强直性脊柱炎诊断中的应用

    张红旗; 龙永梅; 卢晓卉

    2008-01-01

    目的:探讨人类白细胞抗原B27(HLA-B27)检测诊断强直性脊柱炎(AS)的意义.方法:应用微量细胞毒法,对441例AS患者、1167例类风湿性关节炎(RA)患者及100例健康体检者进行HLA-B27对比检测.结果:AS组HLA-B27阳性率为91.6%,RA组阳性率为9.3%,健康体检组阳性率为4.0%,AS组明显高于RA组和体检组,差异有统计学意义(X2=1058.74,P<0.005).男性HLA-B27阳性率(42.4%)明显高于女性(17.8%),差异有统计学意义(X2=63.46,P<0.005).不同年龄组 HLA-B27阳性率有明显差异,30岁以下年龄组明显高于其它年龄组.结论:HLA-B27与AS具有很强的相关性,检测HLA-B27对AS的早期诊断和鉴别具有重要意义.

  20. 外周血白细胞HLA-B27的表达及临床意义

    陈军浩; 张葵

    2001-01-01

    目的观察非强直性脊椎炎与强直性脊椎炎(AS)病人外周血白细胞HLA-B27的表达,探讨各类白细胞HLA-B27表达对AS诊断价值.方法用流式细胞术检测了20例AS和32例非AS患者外周血白细胞HLA-B27的表达.结果对照组各群细胞HLA-B27表达量(以平均荧光强度表示)依次为单核细胞(65.33)、T淋巴细胞(52.55)、淋巴细胞(49.46)和粒细胞(17.02).AS组各群细胞HLA-B27表达均显著高于对照组(P<0.01),依次为单核细胞(337.51)、淋巴细胞(227.38)、T淋巴细胞(268.08)和粒细胞(98.47).对照组与AS组淋巴细胞和T淋巴细胞HLA-B27的的表达未见交叉.结论检测淋巴细胞和T淋巴细胞HLA-B27的表达能最好地区别AS与非AS患者.

  1. Altered regulation of ELAVL1/HuR in HLA-B27-expressing U937 monocytic cells.

    Anna S Sahlberg

    Full Text Available OBJECTIVE: To investigate the role of HLA-B27 expression in the regulation of RNA binding protein (RBP Embryonic Lethal Abnormal Vision (ELAV L1/Human antigen R (HuR expression in Salmonella-infected or LPS-stimulated human monocytic cells, since HuR is a critical regulator of the post-transcriptional fate of many genes (e.g. TNFα important in inflammatory response. METHODS: U937 monocytic cells were stably transfected with pSV2neo resistant vector (mock, wild type HLA-B27, or mutated HLA-B27 with amino acid substitutions in the B pocket. Cells were differentiated, infected with Salmonella enteritidis or stimulated with lipopolysaccharide. The expression levels of HuR protein and cleavage products (CP1 and CP2 were detected by Western blotting and flow cytometry. Specific inhibitors were used to study the role of PKR and p38 in HuR expression and generation of CPs. TNFα and IL-10 secretion after p38 and PKR inhibition were measured by ELISA. RESULTS: Full length HuR is overexpressed and HuR cleavage is disturbed in U937 monocytic cells expressing HLA-B27 heavy chains (HC. Increased full length HuR expression, disturbed cleavage and reduced dependence on PKR after infection correlate with the expression of glutamic acid 45 in the B pocket that is linked to the misfolding of HLA-B27. CONCLUSION: Results show that the expression of HLA-B27 HCs modulates the intracellular environment of U937 monocyte/macrophages by altering HuR regulation. This phenomenon is at least partly dependent on the misfolding feature of the B27 molecule. Since HuR is an important regulator of multiple genes involved in inflammatory response observations offer an explanation how HLA-B27 may modulate inflammatory response.

  2. The application value of HLA-B27 detection in the diagnosis of spondyloarthritis%HLA-B27检测在脊柱关节炎诊断中的应用价值

    姚玮

    2014-01-01

    Objective To analyze human leucocyte antigen B27(HLA-B27) diagnostic value in spondyloarthritis(SpA) .Methods Using flow cytometry to detect HLA-B27 expressions of 298 SpA patients(SpA group) and 195 non-SpA patients(non-SpA group) .Results 227 patients were positive in the 493 patients .In SpA group ,the positive rates of HLA-B27 expressing in ankylo-sing spondylitis (AS ) ,juvenile spondyloarthritis (JSpA ) ,reactive arthritis (ReA ) ,undifferentiated spondyloarthritis (USpA ) , psoriatic arthritis(PsA) were 87 .66% ,59 .09% ,58 .33% ,37 .18% ,25 .00% ,respectively .In non-SpA group ,the positive rates of HLA-B27 expressing in rheumatoid arthritis ,rheumatic arthritis ,cervical or lumbar disease ,osteoarthritis ,gouty arthritis were 18 . 18% ,17 .86% ,16 .67% ,11 .76% ,0 .00% ,respectively .The SpA group and the non-SpA group of HLA-B27 positive comparative differences was statistically significant(P<0 .01) .Conclusion The HLA-B27 is correlated with SpA ,and can provide reference for clinical diagnosis of SpA especially the AS .%目的:分析人类白细胞抗原B27(HLA-B27)在脊柱关节炎(SpA)中的诊断价值。方法采用流式细胞术检测298例SpA患者(SpA组)和195例非SpA患者(非SpA组)HLA-B27的表达水平。结果493例患者中,HLA-B27阳性227例。SpA组中强直性脊柱炎(AS)、幼年脊柱关节炎(JSpA)、反应性关节炎(ReA)、未分化型脊柱关节炎(USpA)和银屑病关节炎(PsA)患者的HLA-B27阳性率,分别为87.66%、59.09%、58.33%、37.18%、25.00%;非SpA组中类风湿关节炎、风湿性关节炎、颈椎或腰椎疾病、骨关节炎、痛风性关节炎患者的HLA-B27阳性率,分别为18.18%、17.86%、16.67%、11.76%、0.00%。SpA组与非SpA组HLA-B27阳性率比较差异有统计学意义(P<0.01)。结论HLA-B27与SpA密切相关,可为临床诊断SpA,尤其是AS提供参考。

  3. A common minimal motif for the ligands of HLA-B*27 class I molecules.

    Alejandro Barriga

    Full Text Available CD8(+ T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA class I molecules. The colossal number of polymorphisms in HLA molecules makes it essential to characterize the antigen-presenting properties common to large HLA families or supertypes. In this context, the HLA-B*27 family comprising at least 100 different alleles, some of them widely distributed in the human population, is involved in the cellular immune response against pathogens and also associated to autoimmune spondyloarthritis being thus a relevant target of study. To this end, HLA binding assays performed using nine HLA-B*2705-restricted ligands endogenously processed and presented in virus-infected cells revealed a common minimal peptide motif for efficient binding to the HLA-B*27 family. The motif was independently confirmed using four unrelated peptides. This experimental approach, which could be easily transferred to other HLA class I families and supertypes, has implications for the validation of new bioinformatics tools in the functional clustering of HLA molecules, for the identification of antiviral cytotoxic T lymphocyte responses, and for future vaccine development.

  4. Intravitreal Triamcinolone Acetonide for Macular Edema in HLA-B27 Negative Ankylosing Spondylitis

    M.M. Moschos

    2010-12-01

    Full Text Available We report a case of a human leukocyte antigen B27 (HLA-B27-negative patient with cystoid macular edema (CME and ankylosing spondylitis (AS after treatment with triamcinolone acetonide. The patient complained of deterioration of visual acuity of the right eye during the last 10 days. At presentation visual acuity of the right eye was 0.2, and the ophthalmic examination did not reveal any sign of active uveitis. Fluorescein angiography (FA and ocular coherent tomography (OCT showed CME. The left eye was normal with a visual acuity of 0.9. Eight weeks after intravitreal injection of triamcinolone acetonide, visual acuity improved to 0.8 and OCT revealed regression of macular edema. Six months later no recurrence was observed. Our case report indicates for the first time that CME may occur in AS independently of the presence of HLA-B27 and intraocular inflammation. Intravitreal use of triamcinolone acetonide can reduce macular edema and restore visual acuity.

  5. A survey to the early and mid-AS patients negative in HLA-B27%HLA-B27表达阴性的早中期强直性脊柱炎患者调查

    刘波; 邱萌

    2011-01-01

    目的:对4年多在我院门诊和病房确诊的早中期强直性脊柱炎(AS)患者进行HLA-B27检测的结果做了对比分析,以了解本地HLA-B27表达阴性与表达阳性的确诊早中期AS患者之间有何差异.方法:采用流式细胞术检测确诊的298例早中期AS患者的HLA-27抗原.研究样本来源于2006年9月~2011年2月在我院临床诊断为早中期AS的患者.结果:临床确诊的早中期AS患者中,HLA-B27表达阴性患者.男女比例约为3.3:1:HLA-B27表达阳性患者,男女比例约为2.9:1,HLA-B27阴性患者与同性别阳性患者平均年龄比较,差异无统计学意义(P>0.05).临床确诊的早中期AS患者中,HLA-B27表达阴性患者各年龄段的阴性率比较,差异无统计学意义(P>0.05),HLA-B27表达阳性患者各年龄段的阳性率比较,差异无统计学意义(P>0.05).结论:本地HLA-B27表达阴性与表达阳性的确诊早中期AS患者之间,男女比例、平均年龄、HLA-B27阳性率和阴性率无显著差异.在临床诊断时,对HLA-B27表达阴性的疑似患者也要给予同样的重视,以免漏诊和误诊.%Objective: To detect HLA-B27 with early and mid ankylosing spondylitis (AS) patients, who were diagnosed during more than four years, then these two results were compared. To find out the difference between HLA-B27 negative and positive expression of AS in patients diagnosed early and mid AS. Methods: Flow cytometry was used to measure HLA-27 antigen in 298 patients diagnosed as early and mid AS. The patients who were diagnosed of early and mid-AS in our hospital from the September 2006 to February 2011 were regarded as study sample. Results: In clinically diagnosed patients with early and mid-AS, the ratio of males to females with HLA-B27 negative expression was about 3.3:1; the ratio of males to females with HLA-B27 positive expression was about 2.9∶1, there were no significant difference in mean age between two groups of HLA-B27 negative patients with the same sex

  6. Characterization of the Recognition Specificity of BH2, a Monoclonal Antibody Prepared against the HLA-B27 Heavy Chain

    Hui-Chun Yu

    2015-04-01

    Full Text Available BH2, a monoclonal antibody prepared against the denatured human leukocytic antigen-B27 heavy chain (HLA-B27 HC, can immunoprecipitate the misfolded HLA-B27 HC complexed with Bip in the endoplasmic reticulum and recognize the homodimerized HLA-B27 HC that is often observed on the cell membrane of patients suffered from ankylosing spondylitis (AS. However, the recognition specificity of BH2 toward the other molecules of HLA-B type and toward the different types of HLA molecules remained uncharacterized. In this study, we carried out the HLA-typing by using the Luminex Technology to characterize the recognition specificity of BH2 and analyzed the binding domain of HLA-B27 HC by BH2. Our results indicated that BH2 preferably binds to molecules of HLA-B and -C rather than HLA-A and the binding site is located within the α2 domain of HLA-B27 HC.

  7. 广西壮族强直性脊柱炎患者HLA-B27亚型的研究

    陈志坚; 李山

    2007-01-01

    目的:对广西壮族强直性脊柱炎(AS)患者进行HLA-B27亚型检测并探讨其临床意义.方法:采用聚合酶链反应-序列特异性引物(PCR-SSP)法对广西壮族65例AS患者和260例健康体检者的HLA-B27进行检测,并对HLA-B27阳性的标本进行亚型分型.结果:AS组的HLA-B27阳性率明显高于对照组(P0.05).结论:广西壮族AS与HLA-B27存在相关性;AS与HLA-B27各亚型的特异基因可能无关.

  8. Determination of HLA-B27 subtypes in patients with ankylosing spondylitis by PCR-SSP%采用PCR-SSP方法检测强直性脊柱炎患者HLA-B27亚型

    韩军艳; 熊平; 严鹏; 邵诗颖; 熊蓓; 吴雄文; 龚非力

    2003-01-01

    目的建立序列特异性引物-聚合酶链方法(PCR-SSP)检测湖北地区人白细胞抗原B27(Human leucocyte antigen-B27, HLA-B27)阳性强直性脊柱炎患者的HLA-B27亚型组成.方法盐析法提取100例HLA-B27阳性的强直性脊柱炎患者外周血基因组DNA,采用PCR-SSP技术分别进行HLA-B位点基因型检测和HLA-B27基因亚型分析.结果 100例标本PCR-SSP扩增均获成功,历时3 h.共检出4种亚型:HLA-B*2704、HLA-B*2711、HLA-B*2715、HLA-B*2722.其中HLA-B*2704纯合子25例、HLA-B*2704杂合子63例;HLA-B*2711杂合子5例;HLA-B*2715杂合子6例;HLA-B*2722杂合子1例.四种亚型所占构成比分别为90.4%、4%、4.8%和0.8%.结论 PCR-SSP方法进行HLA-B27亚型分析,快速、经济、简单;HLA-B*2704是湖北地区强直性脊柱炎患者HLA-B27基因主要亚型.

  9. Erregungsbildung und Erregungsleitung des Herzens bei HLA B27-assozierter juveniler Arthritis in Ruhe und unter körperlicher Belastung

    Sachs, Anke

    2005-01-01

    Eine Herzbeteiligung in Form von Reizleitungsstörungen, Klappenfunktionsstörungen und Funktionsstörungen des Myokards bei erwachsenen Patienten mit HLA B27-positver Spondyloarthropathien ist seit langem bekannt. Überlegungen existieren, dass diese kardialen Veränderungen eher mit der HLA B27-Eigenschaft anstatt mit der Arthritis in Zusammenhang stehen. Der Zeitpunkt, an dem gerade die Reizbildungs- und Reizleitungsstörungen beginnen, ist unklar. Daher verglichen wir in unserer Studie HLA B27-...

  10. Endogenous Processing and Presentation of T-cell Epitopes from Chlamydia trachomatis with Relevance in HLA-B27-associated Reactive Arthritis*

    Cragnolini, Juan J.; García-Medel, Noel; López de Castro, José A.

    2009-01-01

    Chlamydia trachomatis triggers reactive arthritis, a spondyloarthropathy linked to the human major histocompatibility complex molecule HLA-B27, through an unknown mechanism that might involve molecular mimicry between chlamydial and self-derived HLA-B27 ligands. Chlamydia-specific CD8+ T-cells are found in reactive arthritis patients, but the immunogenic epitopes are unknown. A previous screening of the chlamydial genome for putative HLA-B27 ligands predicted multiple peptides that were recog...

  11. Rapid Antigen Processing and Presentation of a Protective and Immunodominant HLA-B*27-restricted Hepatitis C Virus-specific CD8+ T-cell Epitope

    Julia Schmidt; Iversen, Astrid K N; Stefan Tenzer; Emma Gostick; Price, David A.; Volker Lohmann; Ute Distler; Paul Bowness; Hansjörg Schild; Blum, Hubert E.; Paul Klenerman; Christoph Neumann-Haefelin; Robert Thimme

    2012-01-01

    HLA-B*27 exerts protective effects in hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. While the immunological and virological features of HLA-B*27-mediated protection are not fully understood, there is growing evidence that the presentation of specific immunodominant HLA-B*27-restricted CD8+ T-cell epitopes contributes to this phenomenon in both infections. Indeed, protection can be linked to single immunodominant CD8+ T-cell epitopes and functional constraints on e...

  12. Two-dimensional gel analysis demonstrates no structural alteration of HLA-B27 polypeptides between patients with ankylosing spondylitis and healthy individuals.

    Trapani, J A; Walker, I D; McKenzie, I. F.

    1984-01-01

    After precipitation of the HLA-B27 antigen from the surface of peripheral blood lymphocytes (PBL) by means of an anti-HLA-B27 allospecific monoclonal antibody 2-dimensional gel electrophoresis was used to compare the structure of the B27 antigens derived from 5 patients with ankylosing spondylitis with that of healthy HLA-B27 positive counterparts. No significant difference in polypeptide structure was noted, which suggests that the pathogenesis of ankylosing spondylitis does not involve a st...

  13. Serum antibodies from patients with ankylosing spondylitis and Reiter's syndrome are reactive with HLA-B27 cells transfected with the Mycobacterium tuberculosis hsp60 gene.

    Kellner, H; Wen, J.; Wang, J; Raybourne, R B; Williams, K. M.; Yu, D T

    1994-01-01

    HLA-B27-related arthritis is probably mediated by an immune response against HLA-B27 complexed with peptides derived from proteins of arthritis-causing bacteria. Immunogenic proteins with a high degree of homology among bacteria, such as in the hsp60 family, are likely candidates. To create such complexes experimentally, we transfected an HLA-B27 cell line with the Mycobacterium tuberculosis hsp60 gene. Because of previous observations that HLA-B27-peptide complexes can be distinguished by an...

  14. Usage of Conventional PCR Technology for the Detection of HLA-B27 Allele: A Significant Molecular Marker of Ankylosing Spondylitis

    Sharma, Narotam; Sharma, Veena; Masood, Tariq; Nautiyal, Satish Chandra; Sailwal, Shivani; Singh, Rajesh K.; Kushwaha, Rajeev K.; R. K. Singh

    2012-01-01

    Ankylosing spondylitis is a chronic inflammatory disease that has been linked to the human leukocyte antigen class I allele HLA-B27. More than 90 % of patients with ankylosing spondylitis possess the HLA-B27 allele, but only 1 % of people with HLA-B27 develop the disease. Ankylosing spondylitis predominately affects young males. The present study was planned to find out the involvement of HLA-B27 specific allele in relation to age and sex in symptomatic suspected patients of ankylosing spondy...

  15. Low T cell production of TNFα and IFNγ in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism

    Rudwaleit, M; Siegert, S.; Yin, Z; Eick, J; Thiel, A.; Radbruch, A; Sieper, J; Braun, J.

    2001-01-01

    OBJECTIVE—To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon γ (IFNγ), interleukin 4 (IL4), tumour necrosis factor α (TNFα), and IL10 at the single cell level in patients with AS in comparison with healthy HLA-B27 negative and HLA-B27 positive controls.
METHODS—Peripheral blood mononuclear cells from 65 subjects (25 HLA-B27 positive patients with active AS, 18 healthy HLA-B27 positive controls, and...

  16. HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice

    Boucherma, Rachid; Kridane-Miledi, Hédia; Bouziat, Romain;

    2013-01-01

    We have generated a panel of transgenic mice expressing HLA-A*01:03, -A*24:02, -B*08:01, -B*27:05, -B*35:01, -B*44:02, or -C*07:01 as chimeric monochain molecules (i.e., appropriate HLA α1α2 H chain domains fused with a mouse α3 domain and covalently linked to human β2-microglobulin). Whereas...... surface expression of several transgenes was markedly reduced in recipient mice that coexpressed endogenous H-2 class I molecules, substantial surface expression of all human transgenes was observed in mice lacking H-2 class I molecules. In these HLA monochain transgenic/H-2 class I null mice, we observed...... a quantitative and qualitative restoration of the peripheral CD8(+) T cell repertoire, which exhibited a TCR diversity comparable with C57BL/6 WT mice. Potent epitope-specific, HLA-restricted, IFN-γ-producing CD8(+) T cell responses were generated against known reference T cell epitopes after either...

  17. HLA-B27-ASSOCIATED UVEITIS: EPIDEMIOLOGY, CLINICAL PICTURE, AND COMPLICATIONS

    T. V. Dubinina

    2014-01-01

    Full Text Available Anterior uveitis is the most common form of intraocular inflammation. Among them, HLA-B27-associated uveitis occupies one of the leading places, which may be an independent disease or one of the manifestations of spondy- loarthritis (SA. The paper considers the general issues of the nomenclature and classification of uveitis, by using the classification criteria of the International Uveitis Study Group and the Standardization of Uveitis Nomenclature Workshop. The epidemiological aspects of uveitis are described. Emphasis is laid on a difference in the detection rate of uveitis in different countries, in men and women, as well as in different forms of SA. The clinical features of SA- associated uveitis and its complications are discussed. 

  18. 强直性脊柱炎与HLA-B27基因亚型动态定量表达的相关性研究*

    黄建民; 李荣需; 周玲; 陈冬萍; 刘永青; 林周胜

    2013-01-01

    目的:探讨不同HLA-B27基因亚型与强直性脊柱炎的相关性及其动态表达量与强直性脊柱炎疾病活动指数(BASDAI)的关系。方法:收集骨科门诊强直性脊柱炎患者应用流式细胞术定性检测HLA-B27阳性100例,HLA-B27阳性健康对照组30例,通过PCR-SSP(序列引物扩增法)技术检测HLA-B27基因亚型;荧光实时定量RT-PCR技术检测HLA-B27阳性AS患者及HLA-B27阳性健康对照组HLA-B27亚型的mRNA,统计分析两组HLA-B27mRNA表达量及HLA-B27阳性患者HLA-B27mRNA表达水平与强直性脊柱炎患者疾病活动指数的相关性。结果:100例AS患者检出HLA-B2704亚型55例,HLA-B2705亚型45例,30对照组检出HLA-B2704亚型13例, HLA-B2705亚型12例,HLA-B2706亚型3例,HLA-B2709亚型2例;HLA-B27阳性患者HLA-B27mRNA表达水平最低值为1.16,最高值为37.01,均值7.77,HLA-B27阳性健康对照组表达水平最低1.05,最高值2.10,均值为1.51,两组差异有统计学意义(P=0.002);HLA-B27阳性患者HLA-B27mRNA表达水平与强直性脊柱炎患者疾病活动指数密切相关(R=0.707)。结论:本地区AS患者HLA-B27基因亚型以B2704和B2705为主,B2706及B2709可能为保护亚型;HLA-B27阳性患者HLA-B27mRNA 表达水平高于HLA-B27阳性健康者;HLA-B27阳性患者HLA-B27mRNA表达水平与强直性脊柱炎患者疾病活动指数呈正相关。

  19. Körperliche Leistungsfähigkeit bei Patienten mit HLA B27 positiver juveniler idiopathischer Arthritis in Remission

    Fischer, Michael Johannes

    2013-01-01

    Mit dieser Arbeit sollte untersucht werden, ob es eine Beeinträchtigung der körperlichen Leistungsfähigkeit bei Patienten bis zum 20. Lebensjahr mit inaktiver juveniler idiopathischer Arthritis bzw. einer Arthritis in Remission im Vergleich zu gesunden Gleichaltrigen gibt und wenn ja, ob ein Zusammenhang zu dem Eiweißkörper HLA B27 besteht.

  20. HLA-B27 predicts a more extended disease with increasing age at onset in boys with juvenile idiopathic arthritis

    Berntson, Lillemor; Damgård, Michael; Andersson-Gäre, Boel;

    2008-01-01

    OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a heterogeneous condition with very few clinical and laboratory signs that can help predict the course and severity of the disease in the individual patient. The cell-surface antigen HLA-B27 is well known to be associated with spondyloarthropathies...... population-based study as possible. METHODS: We studied an incidence-based cohort of 305 patients collected prospectively in 3 Nordic countries (Sweden, Norway, Denmark). Clinical and serological data of the first 3 years of the disease were collected. RESULTS: HLA-B27 was found to be positive in 25.5% of...... the patients, and we found a higher proportion of HLA-B27-positive boys with older age at disease onset (p=0.034). Regression analysis showed a correlation of 0.7 in the HLA-B27-positive boys, pointing to a higher risk of more joint involvement with older age at disease onset. By Fisher's exact test...

  1. HLA-B27抗原関連急性前部ぶどう膜炎の臨床像についての検討

    菊池, 三季; KIKUCHI, Miki

    1997-01-01

    An objective investigation of the clinical features of HLA-B27-associated acute anterior uveitis (HLA-B27 AAU) was performed using a laser flare cell meter, and by laboratory testing of peripheral blood. The study involved 42 patients (31 men and 11 women, mean age at onset 31.3 years) with HLA-B27 AAU, 33 patients with HLA-B27 negative AAU, and 40 patients with Behcet's disease. The flare intensity was significantly higher at their first attack in HLA-B27(+) patients than in HLA-B27(-) patie...

  2. 强直性脊柱炎疑似患者HLA-B27检测结果分析

    章涛; 方宁; 祁莹; 陈代雄

    2008-01-01

    对111例疑似强直性脊柱炎(AS)患者外周血T淋巴细胞HLA-B27表达进行检测,结合临床资料对AS作出诊断.共检测出HLA-B27阳性49例,总检出率为44%,结合临床资料确诊AS患者46例,包括男性HLA-B27+As患者40例、HLA-B27-AS 3例,女性HLA-B27+AS 2例、HLA-B27-AS 1例,男女患病比为4.4∶1.男性AS确诊患者的HLA-B27阳性率为88%(40/43).提示HLA-B27检测有助于疑似AS病例的确诊.

  3. 465例强直性脊柱炎患者HLA-B27结果的调查分析

    魏云玉; 黄红宇; 陆红兵; 李娟; 马宁

    2008-01-01

    目的 通过对465例强直性脊柱炎患者外周血HLA-B27的检测,了解HLA-B27阴阳性患者在强直性脊柱炎中的情况.方法 用流式细胞术对强直性脊柱炎患者的HLA-B27进行测定.结果 HLA-B27阴性患者占10.5%,HLA-B27阳性患者占89.5%.结论 HLA-B27是诊断强直性脊柱炎的一个重要指标,但不能单独从HLA-B27的阴阳性来判断强直性脊柱炎.还需要结合临床进行综合判断.另外我们还发现HLA-B27阴性强直性脊柱炎患者女性比例较高.

  4. Characterization of a Proteasome and TAP-independent Presentation of Intracellular Epitopes by HLA-B27 Molecules

    Magnacca, A.

    2012-07-17

    Nascent HLA-class I molecules are stabilized by proteasome-derived peptides in the ER and the new complexes proceed to the cell surface through the post-ER vesicles. It has been shown, however, that less stable complexes can exchange peptides in the Trans Golgi Network (TGN). HLA-B27 are the most studied HLA-class I molecules due to their association with Ankylosing Spondylitis (AS). Chimeric proteins driven by TAT of HIV have been exploited by us to deliver viral epitopes, whose cross-presentation by the HLA-B27 molecules was proteasome and TAP-independent and not restricted to Antigen-Presenting Cells (APC). Here, using these chimeric proteins as epitope suppliers, we compared with each other and with the HLA-A2 molecules, the two HLA-B*2705 and B*2709 alleles differing at residue 116 (D116H) and differentially associated with AS. We found that the antigen presentation by the two HLA-B27 molecules was proteasome-, TAP-, and APC-independent whereas the presentation by the HLA-A2 molecules required proteasome, TAP and professional APC. Assuming that such difference could be due to the unpaired, highly reactive Cys-67 distinguishing the HLA-B27 molecules, C67S mutants in HLA-B*2705 and B*2709 and V67C mutant in HLA-A*0201 were also analyzed. The results showed that this mutation did not influence the HLA-A2-restricted antigen presentation while it drastically affected the HLA-B27-restricted presentation with, however, remarkable differences between B*2705 and B*2709. The data, together with the occurrence on the cell surface of unfolded molecules in the case of C67S-B*2705 mutant but not in that of C67S-B*2709 mutant, indicates that Cys-67 has a more critical role in stabilizing the B*2705 rather than the B*2709 complexes.

  5. HLA-B27检测在豫西地区强直性脊柱炎诊断中的意义

    刘好

    2006-01-01

    用特异性人类白细胞抗原(HLA)-B27抗血清对来自豫西地区临床诊断为强直性脊柱炎(AS)的300例患者进行HLA-B27检测.结果HLA-B27阳性率为91%(男性患者为97%,女性为85%).认为AS与HLA-B27相关性强,HLA-B27血清学检测对豫西地区AS患者的诊断和鉴别诊断具有重要意义.

  6. HLA-B27检测在早期脊柱关节病中的诊断作用

    邵标; 王辉

    2008-01-01

    目的 了解HLA-B27在早期脊柱关节病中的诊断作用.方法 采用单克隆抗体血清法对245例早期脊柱关节病人及89例健康者进行HLA-B27检测.结果 245例早期脊柱关节病痛人组中,HLA-B27阳性47例,阳性率为19.18%;其中男性34例,女性13例;89例正常对照组3例HLA-B27阳性,阳性率为3.37%.结论 HLA-B27对早期脊柱关节病患者具有诊断和鉴别诊断作用.

  7. HLA-B27检测在强直性脊柱炎诊断中的临床价值探讨

    刘晖

    2010-01-01

    目的 探讨HLA-B27检测在强直性脊柱炎(AS)诊断中的临床价值.方法 选择我院确诊的AS患者83例作为观察组,随机抽取在我院健康体检人群80例做为对照组,进行HLA-B27检测.结果 观察组HLA-B27阳性率明显高于健康对照组,差异有统计学意义(P<0.01).结论 HLA-B27与AS具有很强的相关性,检测HLA-B27可明显提高诊断特异性.

  8. An HLA-B27 Homodimer Specific Antibody Recognizes a Discontinuous Mixed-Disulfide Epitope as Identified by Affinity-Mass Spectrometry

    Iuraşcu, Marius-Ionuţ; Marroquin Belaunzanar, Osiris; Cozma, Claudia; Petrausch, Ulf; Renner, Christoph; Przybylski, Michael

    2016-04-01

    HLA-B27 homodimer formation is believed to be a hallmark of HLA-B27 associated spondyloarthritides. Recently, we have generated a homodimer-specific monoclonal antibody (HD6) and have demonstrated that HLA-B27 homodimer complexes are present on monocytes of healthy HLA-B27 gene carriers at low levels, with significantly increased levels at active disease. The capability of the HD6 antibody to discriminate between correctly formed HLA-B27 heterotrimers and pathology-associated homodimers is striking and cannot be explained by the primary structure of HLA-B27. We hypothesized that HD6 accesses a unique epitope and used affinity-mass spectrometry for its identification. The HD6 antibody was immobilized on an activated sepharose affinity column, and HLA-B27 homodimer characterized for affinity. The epitope was identified by proteolytic epitope excision and MALDI mass spectrometry, and shown to comprise a discontinuous Cys-203- 257-Cys mixed-disulfide peptide structure that is not accessible in HLA-B27 heterotrimers due to protection by noncovalently linked β2-microglobulin. The epitope peptides were synthesized by solid phase peptide synthesis, and the two monomeric peptide components, HLA-B27(203-219) and HLA-B27(257-273), as well as the homo- and hetero-dimeric disulfide linked combinations prepared. The affinity binding constants KD towards the antibodies were determined using a surface acoustic wave (SAW) biosensor, and showed the highest affinity with a KD of approximately 40 nM to the HD6 antibody for the (203-219)-SS-(257-273) mixed disulfide epitope.

  9. An HLA-B27 Homodimer Specific Antibody Recognizes a Discontinuous Mixed-Disulfide Epitope as Identified by Affinity-Mass Spectrometry

    Iuraşcu, Marius-Ionuţ; Marroquin Belaunzanar, Osiris; Cozma, Claudia; Petrausch, Ulf; Renner, Christoph; Przybylski, Michael

    2016-06-01

    HLA-B27 homodimer formation is believed to be a hallmark of HLA-B27 associated spondyloarthritides. Recently, we have generated a homodimer-specific monoclonal antibody (HD6) and have demonstrated that HLA-B27 homodimer complexes are present on monocytes of healthy HLA-B27 gene carriers at low levels, with significantly increased levels at active disease. The capability of the HD6 antibody to discriminate between correctly formed HLA-B27 heterotrimers and pathology-associated homodimers is striking and cannot be explained by the primary structure of HLA-B27. We hypothesized that HD6 accesses a unique epitope and used affinity-mass spectrometry for its identification. The HD6 antibody was immobilized on an activated sepharose affinity column, and HLA-B27 homodimer characterized for affinity. The epitope was identified by proteolytic epitope excision and MALDI mass spectrometry, and shown to comprise a discontinuous Cys-203- 257-Cys mixed-disulfide peptide structure that is not accessible in HLA-B27 heterotrimers due to protection by noncovalently linked β2-microglobulin. The epitope peptides were synthesized by solid phase peptide synthesis, and the two monomeric peptide components, HLA-B27(203-219) and HLA-B27(257-273), as well as the homo- and hetero-dimeric disulfide linked combinations prepared. The affinity binding constants KD towards the antibodies were determined using a surface acoustic wave (SAW) biosensor, and showed the highest affinity with a KD of approximately 40 nM to the HD6 antibody for the (203-219)-SS-(257-273) mixed disulfide epitope.

  10. Significance of the Expression Quantity of HLA-B27 Gene and Its Subtype in Estimating Patients with Ankylosing Spondylitis%HLA-B27基因表达量及亚型分析在 AS 疾病评估中的意义

    孙灵迪; 王平均; 鹿永; 武晓茜; 邵先安

    2016-01-01

    Objective To investigate whether expression quantity of HLA-B27 and its subtypes associated with incidence of AS,the gene expression of HLA-B27 and its subtypes were detected in patients with AS.Methods 120 cases patients sus-pected with AS and 50 healthy subjects were enrolled in the study.Main demographic and clinical characteristics of the sub-jects were collected.Meanwhile total RNA was isolated from peripheral blood and real time RT-PCR was used to measure the quantitative expression of HLA-B27 gene.Besides RT-PCR,sequence-based typing (SBT)method was used to confirm the HLA-B27 subtype.All experimental data were analyzed by SPSS17.0 software and P values <0.05 were considered to be significant.Results Firstly,there were 55 subjects were finally diagnosed as AS patients among the 120 patients suspec-ted with AS.There were 53 subjects whose HLA-B27 was positive (96.36%)in 55 patients with AS.It showed that there was a correlation between BASDAI and expression quantity of HLA-B27 gene (r=0.845,P =0.000).Five subtypes were found and which were HLA-B27∶04 subtype (29/53,54.72%),HLA-B27:05 subtype (20/53,37.74%),HLA-B27 ∶02 subtype (2/53,3.77%),HLA-B27∶03 subtype (1/53,1.89%)and HLA-B27∶07 subtype (1/53,1.89%),respectively. Among the 50 healthy subjects,there were only one kind of subtype (2/50,4%),which was HLA-B27∶04.There were no statistical difference in the age (t=0.711,P =0.480),sex (χ2 =0.880,P =0.348),family history (χ2 =0.011,P =0.916) and treatment (χ2 =0.113,P =0.736)between the HLA-B27∶04 and HLA-B27∶05 subtypes.Conclusion HLA-B27∶04 and HLA-B27∶05 were primary subtypes in AS patients which HLA-B27 positive.There was a correlation between gene expression quantity of HLA-B27 and AS disease activity index.%目的:探讨人类白细胞抗原(human leukocyto antigens,HLA)B27(HLA-B27)基因表达量及其亚型在强直性脊柱炎疾病诊疗中的意义。方法收集120例疑似强直性脊柱炎患者和50例健康体检

  11. Relationship between Ankylosing Spondylitis and HLA-B27,HLA-Cw and KIRs%HLA-B27、HLA-Cw、KIRs与强直性脊柱炎

    张谷香

    2012-01-01

    强直性脊柱炎(AS)是一种慢性进行性炎症性关节炎,具有明显的家族倾向.虽然,人类白细胞抗原B27(HLA-B27)被认为与AS的发病密切相关,但是由于AS发病机制复杂,HLA-B27仅为导致AS易感的主要基因之一.近年来研究发现,自然杀伤细胞免疫球蛋白样受体(KIRs)和HLA-Cw基因与AS的发生发展也有一定的相关性,且HLA-Cw与活化性/抑制性KIRs之间的失衡可能是影响AS发病机制的关键因素.%Ankylosing spondylitis( AS )is a kind of chronic progressive arthritis which presents clear familial predisposition. Although it has been confirmed that the expression of human leukocyte an-tigen-B27( HLA-B27 )closely related to AS,it is not the only susceptibility genes on AS. Recent studies found that killer immunoglobulin-like receptors( KIR )and HLA-Cw also participated the generation and development of AS. The imbalance between HLA-Cw and activation/inhibition of KIRs might play an important role in the pathogenes is of AS.

  12. The Rate of Helicobacter pylori Seropositivity in a Group of Korean Patients with HLA-B27-Associated Acute Anterior Uveitis.

    Jeong Hun Bae

    Full Text Available To investigate an association between Helicobacter pylori seropositivity and HLA-B27-positive acute anterior uveitis (AAU in Korean patients.Retrospective analysis was performed with data from 106 patients previously diagnosed with AAU without clinical evidence of spondyloarthropathy. Serum immunoglobulin G antibodies to H. pylori were measured by enzyme-linked immunosorbent assay, and HLA typing was performed using polymerase chain reaction of DNA amplification. We included 72 non-uveitis patients and 35 age- and sex-matched healthy controls in the study.Of the 106 patients with AAU, 41 (38.7% were HLA-B27-positive, and 45 (42.5% were seropositive for H. pylori. Patients with HLA-B27-positive AAU had a significantly lower prevalence of H. pylori seropositivity compared to those with HLA-B27-negative AAU and healthy controls (24.4% vs. 53.8%, p = 0.003; 24.4% vs. 57.1%, p = 0.004, respectively. In the non-uveitis group, however, HLA-B27-positive patients exhibited similar H. pylori seropositivity prevalence to HLA-B27-negative patients and healthy controls (45.5% vs. 55.7%, p = 0.529; 45.5% vs. 57.1%, p = 0.497, respectively. In multivariate analysis, a low prevalence of H. pylori seropositivity was significantly associated with HLA-B27-positive AAU (odds ratio = 0.340, 95% confidence interval 0.135-0.855, p = 0.022.Our results suggest an inverse association between H. pylori seropositivity and HLA-B27-positive AAU. Further investigation of this association is needed, given the low prevalence of H. pylori seropositivity observed in patients with HLA-B27-positive AAU.

  13. Microarray Analysis of Response of Salmonella during Infection of HLA-B27- Transfected Human Macrophage-Like U937 Cells

    Hinton Jay CD; He Qiushui; Danino Vittoria; Ge Shichao; Granfors Kaisa

    2010-01-01

    Abstract Background Human leukocyte antigen (HLA)-B27 is strongly associated with the development of reactive arthritis (ReA) in humans after salmonellosis. Human monocytic U937 cells transfected with HLA-B27 are less able to eliminate intracellular Salmonella enterica serovar Enteritidis than those transfected with control HLA antigens (e.g. HLA-A2). To investigate further the mechanisms by which HLA-B27-transfected cells allow increased replication of these bacteria, a DNA-based microarray ...

  14. HLA-B27 Modulates Intracellular Growth of Salmonella Pathogenicity Island 2 Mutants and Production of Cytokines in Infected Monocytic U937 Cells

    Shichao Ge; Qiushui He; Kaisa Granfors

    2012-01-01

    BACKGROUND: Salmonella enterica serovar Enteritidis PT4 KS8822/88 replicates rapidly in HLA-B27-transfected human monocytic U937 cells. In this process, Salmonella pathogenicity island 2 (SPI-2) genes play a crucial role. Our previous study indicated that 118 Salmonella genes, including 8 SPI-2 genes were affected by HLA-B27 antigen during Salmonella infection of U937 cells. METHODS/PRINCIPAL FINDINGS: To further investigate Salmonella replication in HLA-B27-positive U937 monocytic cells, two...

  15. Autoantibodies to the HLA-B27 sequence cross-react with the hypothetical peptide from the arthritis-associated Shigella plasmid.

    Tsuchiya, N.; Husby, G; Williams, R. C.; Stieglitz, H; Lipsky, P E; Inman, R.D.

    1990-01-01

    We previously reported elevated serum antibody levels to a peptide representing the HLA-B27 polymorphic region (B27 peptide) in HLA-B27(+) ankylosing spondylitis (AS) patients. A plasmid (pHS-2) isolated from arthritogenic Shigella flexneri strains had been shown to encode an amino acid sequence homologous to HLA-B27. Rabbit antibody to this sequence (pHS-2 peptide) strongly cross-reacted with B27 peptide and, to a much lesser extent, with Klebsiella nitrogenase peptide. Serum antibody levels...

  16. Expression of arthritis-causing HLA-B27 on Hela cells promotes induction of c-fos in response to in vitro invasion by Salmonella typhimurium.

    Ikawa, T; Ikeda, M; Yamaguchi, A; Tsai, W.C.; Tamura, N; Seta, N; Trucksess, M; Raybourne, R B; Yu, D T

    1998-01-01

    HLA-B27 confers a very strong genetic predisposition to development of a reactive arthritis after infection by bacteria such as Salmonella typhimurium. This study examines the role of HLA-B27 in the initiation of the earliest host activities after exposure to Salmonella, namely activation of the immediate early genes in the epithelial cells. Our major finding is that in Hela cells, the expression of c-fos was induced by Salmonella invasion only when the cells expressed the transfected HLA-B27...

  17. Ultrasonographic Assessment of Enthesitis in HLA-B27 Positive Patients with Rheumatoid Arthritis, a Matched Case-Only Study

    Antonio Mera-Varela; Aida Ferreiro-Iglesias; Eva Perez-Pampin; Marisol Porto-Silva; Gómez-Reino, Juan J.; Antonio Gonzalez

    2013-01-01

    INTRODUCTION: HLA-B27 has a modifier effect on the phenotype of multiple diseases, both associated and non-associated with it. Among these effects, an increased frequency of clinical enthesitis in patients with Rheumatoid Arthritis (RA) has been reported but never explored again. We aimed to replicate this study with a sensitive and quantitative assessment of enthesitis by using standardized ultrasonography (US). METHODS: The Madrid Sonography Enthesitis Index (MASEI) was applied to the US as...

  18. Application of a Simple In-House PCR-SSP Technique for HLA-B* 27 Typing in Spondyloarthritis Patients

    Parasannanavar, Devraj J.; Anjali Rajadhyaksha; Kanjaksha Ghosh

    2013-01-01

    Background. Microlymphocytotoxicity (MLCT) and flowcytometry (FC) are the conventional serological methods to detect HLA-B* 27. Due to some disadvantages in these methods, most of the HLA laboratories have now switched over to molecular methods. Molecular techniques based on commercial kits are expensive; as such many laboratories with limited funds in developing countries cannot afford these techniques. Aims. Our main aim was to standardize a simple inexpensive in-house PCR-SSP technique for...

  19. Alteration of HLA-B27 Peptide Presentation after Infection of Transfected Murine L Cells by Shigella flexneri

    Boisgérault, Florence; Mounier, Joëlle; Tieng, Vannary; Stolzenberg, Marie-Claude; Khalil-Daher, Iman; Schmid, Michel; Sansonetti, Philippe; Charron, Dominique; Toubert, Antoine

    1998-01-01

    Shigella flexneri is a triggering agent for reactive arthritis in HLA-B27-susceptible individuals. Considering the intracellular multiplication of bacteria, it seems likely that bacterial peptides may be presented by the major histocompatibility complex (MHC) class I pathway. To examine this hypothesis, we infected HLA-B*2705- and/or human β2-microglobulin-transfected murine L-cell lines with M90T, an invasive strain of S. flexneri. Bacterial infection induced no detectable modifications in t...

  20. Validity of magnetic resonance image and HLA-B27 in early detection of sacroiliitis in Egyptian spondyloarthropathic patients

    El-Shereef, Rawhya R.; Amal Ali; Ayman Darwish; Fatma Ali; Mohammed Ibrahim; Lamia Hamdy

    2015-01-01

    Objective The aim of this study was to compare the validity of MRI in the early detection of sacroiliitis with laboratory findings of human leukocyte antigen-B27 (HLA-B27), conventional radiography, and clinical assessment. Participants and methods Sixty patients with spondyloarthropathy (group II) with duration of illness less than 2 years and 20 healthy controls (group I) were included in this study. Both groups were subjected to assessment of history, clinical examination, and lab...

  1. Vision-Related Quality of Life in Patients with Inactive HLA-B27-Associated-Spectrum Anterior Uveitis.

    Hoeksema, Lisette; Los, Leonoor I

    2016-01-01

    We investigated the vision-related quality of life (VR-QOL) in patients with HLA-B27 associated anterior uveitis (AU). The study was conducted in 2012 at the ophthalmology department of the University Medical Center of Groningen. We included AU patients who were HLA-B27 positive and/or were diagnosed by a rheumatologist with an HLA-B27 associated systemic disease. Sixty-one of 123 (50%) adult patients participated. All patients filled-out the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25), Beck Depression Inventory (BDI-II), social support lists and an additional questionnaire for gathering general information. Medical records were reviewed for clinical characteristics. Analyses were conducted on various patient and ocular characteristics. We compared our NEI VFQ-25 scores with those previously found in the literature. Our main outcome measures were VR-QOL scores and their associations with various general patient and ocular characteristics. We found that the NEI VFQ-25 mean overall composite score was 88.9±8.8, which is relatively high, but lower than that found in a normal working population. The mean general health score was 47.4±20.8, which is lower than in patients with other ocular diseases. Patients with a systemic disease scored significantly lower on general health and VR-QOL, compared to patients without a systemic disease. Patients with a depression (6/59 (10%)) frequently had ankylosing spondylitis (5/6 patients) and they scored significantly worse on VR-QOL. We concluded that patients with HLA-B27 associated AU have a relatively high VR-QOL. However, the presence of a systemic disease is associated with lower VR-QOL and general health scores. In addition, depression is associated with a lower VR-QOL. PMID:26808922

  2. Structural analysis of an HLA-B27 functional variant, B27d detected in American blacks

    The structure of a new functional variant B27d has been established by comparative peptide mapping and radiochemical sequencing. This analysis complete the structural characterization of the six know histocompatibility leukocyte antigen (HLA)-B27 subtypes. The only detected amino acid change between the main HLA-B27.1 subtype and B27d is that of Try59 to His59. Position 59 has not been previously found to vary among class I HLA or H-2 antigens. Such substitution accounts for the reported isoelectric focusing pattern of this variant. HLA-B27d is the only B27 variant found to differ from other subtypes by a single amino acid replacement. The nature of the change is compatible with its origin by a point mutation from HLB-B27.1. Because B27d was found only American blacks and in no other ethnic groups, it is suggested that this variant originated as a result of a mutation of the B27.1 gene that occurred within the black population. Structural analysis of B27d was done by comparative mapping. Radiochemical sequencing was carried out with 14C-labeled and 3H-labeled amino acids

  3. Application of a Simple In-House PCR-SSP Technique for HLA-B* 27 Typing in Spondyloarthritis Patients

    Devraj J. Parasannanavar

    2013-01-01

    Full Text Available Background. Microlymphocytotoxicity (MLCT and flowcytometry (FC are the conventional serological methods to detect HLA-B* 27. Due to some disadvantages in these methods, most of the HLA laboratories have now switched over to molecular methods. Molecular techniques based on commercial kits are expensive; as such many laboratories with limited funds in developing countries cannot afford these techniques. Aims. Our main aim was to standardize a simple inexpensive in-house PCR-SSP technique for HLA-B* 27 typing. Materials and Methods. Sequence Specific primers were designed to amplify all the subtypes of B* 27 using IMGT-HLA sequence database. Accuracy was checked by retyping of 90 PCR-SSOP typed controls. Results. The presence of 149 bp specific band with control band on 2% agarose gel showed B* 27 positivity. No discrepancies were found when compared with PCR-SSOP results. The frequency of HLA-B* 27 was found to be significantly increased (68.75% versus 4.40%, O.R 46.909: P value 6.62E-32 among 700 SpA patients as compared to controls. Clinically, 54% of patients had polyarticular arthritis with SI joints involvement (68% and restricted spine flexion (60%. Conclusion. In-house PCR-SSP technique is very simple and inexpensive technique to detect B* 27 allele, which was strongly associated with SpA patients from Western India.

  4. Structural analysis of an HLA-B27 functional variant, B27d detected in American blacks

    Rojo, S.; Aparicio, P.; Hansen, J.A.; Choo, S.Y.; Lopez de Castro, J.A.

    1987-11-15

    The structure of a new functional variant B27d has been established by comparative peptide mapping and radiochemical sequencing. This analysis complete the structural characterization of the six know histocompatibility leukocyte antigen (HLA)-B27 subtypes. The only detected amino acid change between the main HLA-B27.1 subtype and B27d is that of Try/sub 59/ to His/sub 59/. Position 59 has not been previously found to vary among class I HLA or H-2 antigens. Such substitution accounts for the reported isoelectric focusing pattern of this variant. HLA-B27d is the only B27 variant found to differ from other subtypes by a single amino acid replacement. The nature of the change is compatible with its origin by a point mutation from HLB-B27.1. Because B27d was found only American blacks and in no other ethnic groups, it is suggested that this variant originated as a result of a mutation of the B27.1 gene that occurred within the black population. Structural analysis of B27d was done by comparative mapping. Radiochemical sequencing was carried out with /sup 14/C-labeled and /sup 3/H-labeled amino acids.

  5. The asymmetric protein expression hypothesis - Explaining the unilaterality of HLA-B27-positive acute anterior uveitides.

    Clarke, Margo S; Plouznikoff, Alexandre; Deschênes, Jean

    2016-03-01

    For reasons still unclear, most HLA-B27-positive acute anterior uveitides occur unilaterally. Building upon the growing literature showing that left-right asymmetry exist at the biomolecular and at the cellular levels, we propose a new hypothesis to explain why HLA-B27-positive acute anterior uveitides tend to affect one eye selectively. We postulate that left and right uveal tissue may present quantitatively and qualitatively different proteins to the immune system, capable to trigger an autoimmune response, and that other variables, including anatomical, cellular and molecular barriers, as well as our own eye-derived immunological tolerance and immune suppressive intraocular microenvironment may also be unequally distributed, and impact differently the immune privileges of the left and right eye. These same quantitative and qualitative differences might also explain why HLA-B27-positive acute anterior uveitides can flip-flop between the left and the right eye, after the first attack. By trying to figure out why one eye is targeted by an autoimmune reaction while the other is clinically unaffected, we might be able to better understand how and why an autoimmune reaction starts. Hopefully, this will help us devise better treatments for ocular autoimmune diseases, and contribute to the management of autoinflammatory conditions with a marked asymmetric clinical presentation in other fields. PMID:26880626

  6. 广东潮州地区强直性脊柱炎患者 HLA-B27的检测与临床相关性研究%Investigation of the relationship between clinical manifestation of ankylosing spondylitis and HLA-B27 antigen in Chaozhou, Guangdong Province

    刘潮坚; 蔡拉加; 石昭宏; 林剑雄

    2013-01-01

      目的检测强直性脊柱炎(Ankylosing spondylitis,AS)患者 HLA-B27抗原表达情况,并分析其与临床情况的关系.方法选择我院2008年5月到2011年5月期间150例 AS 患者,按 HLA-B27抗原表达分为两组:HLA-B27阳性组(n=108)及 HLA-B27阴性组(n=42).分别检测两组血标本血沉、C 反应蛋白、α1-酸性糖蛋白水平,并检查心电图、骨盆正位片和腰椎正侧位,比较两组的发病年龄、性别比、临床症状.结果① HLA-B27阴性组以31~45岁年龄段为主(占阴性组52.4%),阳性组以16~30岁年龄段为主(占阳性组57.4%);② HLA-B27阳性组较阴性组全身症状更为严重(P0.05);③ HLA-B27阴性组较多表现为在窦缓和/或传导阻滞,而 HLA-B27阳性组则较多表现为左室高电压(P0.05).结论 AS 患者临床症状与 HLA-B27抗原有很高的相关性,HLA-B27抗原阴性患者与阳性患者相比病情较轻,预后较好.%Objective To investigate the relationships between clinical manifestation of ankylosing spondylitis (AS) and HLA-B27 antigen by analyzing the expression level of HLA-B27 antigen. Methods During May 2008 and May 2011, 150 AS patients attended our study. According to the expression level of HLA-B27 antigen, these patients were classified into two groups: HLA-B27 negative group and HLA-B27 positive group. The erythrocyte sedimentation rate (ESR), CRP, and α1-AGP, electrocardiogram, anterioposterior radiograph of pelvis, anterior and lateral lumbar vertebral X ray were also examined. The age of onset, sex proportion, and clinical manifestation were compared in the two groups. Results ① HLA-B27 negative expression mainly ranged from 31 to 45 years old (52.4%), but positive expression group mainly ranged from 16 to 30 years old (57.4%). ② The rate of systemic symptom such as fever, night sweat, and fatigue were higher in HLA-B27 positive group than that in negative group(P0.05). ③ The major clinical symptom in HLA-B27 negative patients were sinus

  7. The Combination of MR Imaging and HLA-B27 on the Diagnosis of Sacroiliac Joints Lesions in Ankylosing Spondylitis%MRI与HLA-B27诊断强直性脊柱炎骶髂关节病变的联合应用

    王东; 江华堂; 陈武标; 吴永峻

    2012-01-01

    目的 探讨MRI与HLA-B27联合对诊断强直性脊柱炎(AS)骶髂关节(SIJ)病变的临床应用价值.方法 回顾性分析48例经临床确诊的AS的MRI和HLA-B27检测资料,并比较MRI与MRI联合HLA-B27对AS SIJ病变诊断的阳性率.结果 48例AS病例中,MRI检查诊断AS的阳性率为79.2%;HLA-B27检测阳性率为89.6%;MRI联合HLA-B27检测阳性为91.7%; MRI联合HLA-B27诊断AS的阳性率高于单纯MRI检查组,其差异有统计学意义(x2=11.759,P<0.01).结论 MRI与HLA-B27联合可提高AS诊断的阳性率,有利于AS的早期发现、及时治疗.%Objective To investigate the clinical value of combination of MR imaging and HLA-B27 on the diagnosis of sacroiliac joints (SIJ) lesions in ankylosing spondylitis (AS). Methods The MRI and HLA-B27 data of 48 AS cases proved by clinical examination were retrospectively analyzed. The positive rates in detecting the SIJ lesions of AS were compared between MRI and combination MRI and HLA-B27. Results Among the 48 patient of AS, the positive rate of MRI diagnosis was 79.2%, the positive rate of HLA-B27 examination was 89.6%, the positive rate of MRI combined with HLA-B27 was 91.7%. The positive rate of MRI combined with HLA-B27 was higher than that of MRI, which were showing significant difference (X2=1.759, P < 0.01). Conclusion The combination of MRI and HLA-B27 examination can increase the positive rate of AS diagnosis, which may be helpful for AS early detection and prompt treatment.

  8. Antibody activity in ankylosing spondylitis sera to two sites on HLA B27.1 at the MHC groove region (within sequence 65-85), and to a Klebsiella pneumoniae nitrogenase reductase peptide (within sequence 181-199)

    1990-01-01

    74 overlapping peptides of varying lengths from Klebsiella pneumoniae nitrogenase reductase (residues 181-199) and from the HLA B27.1 molecule (residues 65-85) were synthesized and tested by ELISA against sera from HLA B27+ ankylosing spondylitis (AS) patients, and sera from HLA B27+ and HLA B27- healthy first-degree relatives. Antibody activity in AS sera to Klebsiella peptides of four to eight amino acids was maximal with the peptide NSRQTDR. Activity to HLA B27 peptides was maximal with th...

  9. The value of combination of magnetic resonance imaging and HLA-B27 in early diagnosis of ankylosing spondylitis%磁共振联合HLA-B27诊断早期强直性脊柱炎的应用价值

    孔庆聪; 邵硕; 刘卫敏; 王晓红; 林云崖; 单鸿

    2012-01-01

    目的 探讨MRI联合HLA-B27抗原检测骶髂关节强直性脊柱炎(AS)早期诊断的临床价值.方法 回顾性分析经临床确诊的35例早期AS患者,均行骶髂关节X线、MRI检查及HLA-B27抗原检测,并分别比较骶髂关节MRI、HLA-B27、骶髂关节MRI联合HLA-B27的阳性率.结果 35例早期强直性脊柱炎患者中,通过MRI检查诊断早期强直性脊柱炎的阳性率为74.3%(26/35例),HLA-B27阳性率为88.6%(31/35例),骶髂关节MRI联合HLA-B27的阳性率为97.1%(34/35例),其中MRI联合HLA-B27的阳性检出率高于MRI有统计学意义(P=0.013),MRI与HLA-B27、MRI联合HLA-B27HLA-B27的阳性检出率比较无统计学意义(P>0.05).结论 骶髂关节MRI联合HLA-B27检查能提高早期强直性脊柱炎的阳性检出率,有利于临床早期诊断、早期治疗.%Objective To explore the clinical value of combination of Magnetic Resonance Imaging! MRI) and HLA-B27 in early diagnosis of ankylosing spondylitis (AS). Methods 35 patients with early AS proven by clinical examination were included in this study. All patients underwent X-ray,MRI and HLA-B27 examination before treatment. The positive rates in detecting AS were compared between MRI and combination MR imaging and HLA-B27. Results Among the 35 patients of early AS, only 26 (74. 3%) were diagnosed to be early AS by MRI,the positive rate of HAL-B27 was 88. 6% ,the positive rate of MRI combined with HLA-B27 was 97. 1% . The positive rate of MRI combined with HLA-B27 was significantly higher than that of MRI (P = 0. 013 ) . While thepositive rates were not statistically significant between MRI and HLA-B27,and between MRI combined with HLA-B27and HLA-B27 alone (P>0. 05). Conclusion Combination of MRI examination and HLA-B27 can improve the detecting rate early of AS.

  10. Comparison of Clinical Features in Ankylosing Spondylitis Patients with HLA-B27 Negative Expression and Positive Expression%HLA-B27阴性和阳性强直性脊柱炎患者临床情况比较

    刘波; 胡友红

    2011-01-01

    Objective To compare the clinical situation of the patients diagnosed as ankylosing spondylitis( AS ) with negative expression and positive expression of human leukocyte antigen B27( HLA-B27 ).Methods Use flow cytometry to measure HLA-B27 among the 301 patients diagnosed as AS in our hospital . And a comparative analysis has been done between the HLA-B27 negative and HLA-B27 positive patients.Results ①The incidence in male was significantly higher than in female in HLA-B27 negative expression group and positive expression group. The average onset age of HLA-B27-negative patients are older than those of the positive ones of the same sex; ②The age of the patients with HLA-B27 negative expression was mainly 31 ~45,and the positive ones 16 ~30. ③The major first symptoms of both the positive and negative patients were axial and peripheral arthritis. The major clinical symptoms include low back pain and hip pain. The rate of systemic symptom such as fever, night sweat and fatigue in negative patients was significant lower than that in the positive group. Conclusion The average age and onset age of HLA-B27-negative patients are older than those of the positive ones of the same sex,and part of HLA-B27 negative patients'condition was relatively mild. The different clinical features of HLA-B27 negative expression and positive expression patients call for due attention in diagonosing suspected AS patients with negative HLA-B27 expression.%目的 比较HLA-B27检测阴性与阳性的确诊强直性脊柱炎(AS)患者临床情况.方法 用流式细胞仪对在本院确诊的301例AS患者进行人类白细胞抗原B27(HLA-B27)检测,并对HLA-B27阴性和阳性患者进行比较研究.结果 ①HLA-B27阴性和阳性患者男性发病率明显高于女性,阴性与同性别阳性患者平均发病年龄明显偏晚.②HLA-B27阴性患者以31~45岁为主,阳性患者以16~30岁为主.③HLA-B27阴性和阳性患者首发症状均以中轴关节炎和外周关节

  11. Value of Combination Detection of HLA-B27 and Sacroiliac Joint CT Scanning in Diagnosis of Ankylosing Spondylitis%骶髂关节CT及HLA-B27联合检测在强直性脊柱炎诊断中的价值

    王红; 金笛; 肖红霞

    2012-01-01

    Objective To study the relativity between the feature of sacroiliac joint CT and the positive rate of HLA - B27 in the e-raly diogonosis of ankylosing spondylitis, in order to improve the diagnostic level of the ankylosing spondylitis. Methods Sacroiliac joint CT features and the positive rate of HLA - B27 of 162 cases diagnosed as ankylosing spondylitis were collectively analysed. Results 6. 2% of sacroiliac joints CT of 162 patients were normal but 93. 8% abnormal. Positive rate of HLA - B27 was 84% . Cases simultaneously existing both HLA - B27 posibility and abnormity of sacroiliac joints CT were 79% , but cases of HLA - B27 negativity and abnormity of sacroiliac joints CT were 14. 8% . Cases of HLA - B27 positive but sacroiliac joints CT normal were 6. 2% . Compared with the result of HLA - B27 and sacroilial joint CT,x2 =2.118,P>0.01. Conclusion HLA - B27 and sacroiliac joints CT are important reference indicators for diagnosing ankylosing spondylitis. The correspondence between the results of HLA - B27 and the sacroiliac joint CT is high. There is no significant differences in two kinds of results. Detection of HLA - B27 in combination of clinical symptoms is beneficial for early diagnosis. Characteristics of sacroiliac joints CT could be used as important foundation in early, developing and late phases.%目的 探讨骶髂关节CT及HLA-B27联合检测在强直性脊柱炎早期诊断中的应用,以提高强直性脊柱炎的诊断水平.方法 分析经临床诊断为强直性脊柱炎的162例患者HLA-B27的阳性率及骶髂关节CT的特点,对其结果进行总结性分析.结果 162例患者中骶髂关节CT异常者占93.8%.HLA-B27阳性率为85.2%.HLA-B27阳性及骶髂关节CT异常表现并存占79%;HLA-B27阴性、骶髂关节异常占14.8%;HLA-B27阳性而骶髂关节正常者6.2%.HLA-B27与骶髂关节CT两种结果比较,x2 =2.118,P >0.01.结论 HLA-B27及骶髂关节CT是诊断强直性脊柱炎的重要参考指标.诊断AS的HLA-B

  12. HLA-B27检测应用于强直性脊柱炎的诊断价值分析

    梁小亮

    2011-01-01

    目的:探讨HLA-B27检测对强直性脊柱炎的诊断价值.方法:58例患者作为试验组,另选择58例健康人士作为对照组,对比分析两组HLA-B27阳性率试结果:HLA-B27阳性率实验组为91.37%,对照组为6.90%,两组比较差异有显著性(X2=79.472,P<0.01).结论:HLA-B27检测用于强直性脊柱炎的诊断,可提供重要的参考指标,从而进一步提高确诊率.

  13. HLA-B27-Transfected (Salmonella Permissive) and HLA-A2-Transfected (Salmonella Nonpermissive) Human Monocytic U937 Cells Differ in Their Production of Cytokines

    Ekman, Päivi; Saarinen, Marja; He, Qiushui; Gripenberg-Lerche, Christel; Grönberg, Alvar; Arvilommi, Heikki; Granfors, Kaisa

    2002-01-01

    The cytokine secretion of the Salmonella-permissive, HLA-B27-positive U937 cells was examined, as it was previously shown that these cells kill Salmonella less efficiently than controls. Salmonella-permissive U937 cells showed upregulated production of interleukin 10 and to a lesser extent tumor necrosis factor alpha. HLA-B27-associated modulation of cytokine responses may have importance in the pathogenesis of reactive arthritis.

  14. HLA-B27 modulates intracellular growth of Salmonella pathogenicity island 2 mutants and production of cytokines in infected monocytic U937 cells.

    Shichao Ge

    Full Text Available BACKGROUND: Salmonella enterica serovar Enteritidis PT4 KS8822/88 replicates rapidly in HLA-B27-transfected human monocytic U937 cells. In this process, Salmonella pathogenicity island 2 (SPI-2 genes play a crucial role. Our previous study indicated that 118 Salmonella genes, including 8 SPI-2 genes were affected by HLA-B27 antigen during Salmonella infection of U937 cells. METHODS/PRINCIPAL FINDINGS: To further investigate Salmonella replication in HLA-B27-positive U937 monocytic cells, two SPI-2 genes, ssaS and sscA up-regulated most during Salmonella infection of HLA-B27-transfected U937 cells, were mutated by using one-step gene disruption method. Intracellular survival and replication of the mutants in the U937 cells was compared to that of the wild type strain. Surprisingly, the two mutated strains replicated significantly more than the wild type bacteria in HLA-B27-transfected cells. Secretion of tumor necrosis factor alpha (TNF-α and interleukin 10 (IL-10 was significantly induced during the infection of HLA-B27-transfected U937 cells with the mutants. The results indicated that the certain SPI-2 genes in wild type bacteria suppress Salmonella intracellular growth and production of cytokines in infected HLA-B27-transfected cells. HLA-B27-associated modulation of Salmonella SPI-2 genes and cytokine production may have importance in the persistent infection of the bacteria and the pathogenesis of reactive arthritis. CONCLUSIONS: The study provides evidence that certain virulence factors of pathogens can reduce the intracellular growth in the host cells. We suggest that the limiting intracellular growth might be a strategy for persistence of bacteria in host cells, keeping a balance between pathogenic growth and pathogenesis.

  15. Peptide Handling by HLA-B27 Subtypes Influences Their Biological Behavior, Association with Ankylosing Spondylitis and Susceptibility to Endoplasmic Reticulum Aminopeptidase 1 (ERAP1)*

    García-Medel, Noel; Sanz-Bravo, Alejandro; Alvarez-Navarro, Carlos; Gómez-Molina, Patricia; Barnea, Eilon; Marcilla, Miguel; Admon, Arie; de Castro, José A. López

    2014-01-01

    HLA-B27 is strongly associated with ankylosing spondylitis (AS). We analyzed the relationship between structure, peptide specificity, folding, and stability of the seven major HLA-B27 subtypes to determine the role of their constitutive peptidomes in the pathogenicity of this molecule. Identification of large numbers of ligands allowed us to define the differences among subtype-bound peptidomes and to elucidate the peptide features associated with AS and molecular stability. The peptides iden...

  16. Interaction between HLA-B60 and HLA-B27 as a Better Predictor of Ankylosing Spondylitis in a Taiwanese Population.

    James Cheng-Chung Wei

    Full Text Available Ankylosing spondylitis (AS is a form of chronic inflammatory spondyloarthritis (SpA that causes pain and stiffness in spines or joints. Human leukocyte antigen B27 (HLA-B27 and B60 (HLA-B60 have been reported as major genetic risk factors of AS. In addition, rs13202464, located on major histocompatibility complex (MHC region, showed high sensitivity (98.7% and specificity (98.0% for HLA-B27.The aim of our study is to test whether the interaction between HLA-B60 and HLA-B27 (rs13202464 can serve as a better predictor of AS. We have genotyped HLA-B60 and rs13202464 among 471 patients with AS and 557 healthy subjects. Combined risk factors were investigated to test the biological interaction.Our results indicated that the relative risk (RR for HLA-B27+/HLA-B60- was 152 (95% CI 91 to 255 and it increased to 201 (95% CI 85 to 475 in HLA-B27+/HLA-B60+ patients (with HLA-B27-/HLA-B60- as reference. Combinational analysis of two risk factors (HLA-B27+/HLA-B60+ showed a relative excess risk due to interaction (RERI of 46.79 (95% CI: -117.58 to 211.16, attributable proportion (AP of 0.23 (95% CI: -0.41 to 0.88 and a synergy index (S of 1.31 (95% CI: 0.56 to 3.04.In conclusion, genetic interaction analysis revealed that the interaction between HLA-B60 and HLA-B27 is a better marker for the risk of AS susceptibility in a Taiwanese population.

  17. 微量淋巴细胞毒法检测HLA-B27试验的质控体会

    岳文勇

    2008-01-01

    @@ 国内外研究表明,强直性脊柱炎(AS)患者HLA-B27抗原阳性率为83%~95.19%[1,2].对患者进行HLA-B27检测已经成为临床排除、提示或预防强直性脊柱炎的一个重要的辅助手段.

  18. HLA-B 27在强直性脊柱炎诊断中的应用效果评价

    张斓

    2015-01-01

    目的 探讨HLA-B27在强直性脊柱炎(AS)诊断中的应用效果.方法 随机抽取53例AS患者的临床资料,作为观察组.选取同时期进行健康体检的志愿者53例作为对照组.抽取被研究者空腹血2 mL,均匀混合,抗凝完全.存于4℃冰箱,4 d内检测均有效.采取微量细胞毒法检测HLA-B27水平.观察HLA-B27阳性检出率.结果 观察组患者HLA-B27阳性检出率为92.45%,对照组HLA-B27阳性检出率为0.00%,2组HLA-B27阳性检出率比较,差异有统计学意义(P<0.05).观察组患者HLA-B 27诊断敏感度为92.45%(49/53),特异度为100.00%(53/53),诊断正确率为96.23%.结论 HLA-B27可作为AS的诊断依据,辅助临床诊断.

  19. 闽南地区强直性脊柱炎与HLA-B27关联性的观察

    洪素云; 周娟娟; 裴斌; 谢金镇

    2005-01-01

    目的:探讨闽南地区HLA-B27对强直性脊柱炎的诊断意义.方法:用特异性HLA-B27抗血清对临床疑似强直性脊柱炎的患者 1 500 例和 1 500 名健康者进行HLA-B27检测.结果:疑似强直性脊柱炎患者 1 500 例,其中男性 1 212 例,女性288 例,男女比例约为4:1.B27阳性率为 67.07%,其中男性 70.05%(849/1212),女性 54.51%.发病年龄主要集中在青少年时期.1 500 名健康者中HLA-B27阳性39例,阳性率为 2.6%.结论:AS与HLA-B27相关性强,HLA-B27血清学检测对强直性脊柱炎的诊断和鉴别诊断具有重要意义.

  20. Human Leukocyte Antigen (HLA) B27 Allotype-Specific Binding and Candidate Arthritogenic Peptides Revealed through Heuristic Clustering of Data-independent Acquisition Mass Spectrometry (DIA-MS) Data.

    Schittenhelm, Ralf B; Sivaneswaran, Saranjah; Lim Kam Sian, Terry C C; Croft, Nathan P; Purcell, Anthony W

    2016-06-01

    Expression of HLA-B27 is strongly associated with ankylosing spondylitis (AS) and other spondyloarthropathies. While this is true for the majority of HLA-B27 allotypes, HLA-B*27:06 and HLA-B*27:09 are not associated with AS. These two subtypes contain polymorphisms that are ideally positioned to influence the bound peptide repertoire. The existence of disease-inducing peptides (so-called arthritogenic peptides) has therefore been proposed that are exclusively presented by disease-associated HLA-B27 allotypes. However, we have recently demonstrated that this segregation of allotype-bound peptides is not the case and that many peptides that display sequence features predicted to favor binding to disease-associated subtypes are also capable of being presented naturally by protective alleles. To further probe more subtle quantitative changes in peptide presentation, we have used a combination of data-independent acquisition (DIA) and multiple reaction monitoring (MRM) mass spectrometry to quantify the abundance of 1646 HLA-B27 restricted peptides across the eight most frequent HLA-B27 allotypes (HLA-B*27:02-HLA-B*27:09). We utilized K means cluster analysis to group peptides with similar allelic binding preferences across the eight HLA-B27 allotypes, which enabled us to identify the most-stringent binding characteristics for each HLA-B27 allotype and further refined their existing consensus-binding motifs. Moreover, a thorough analysis of this quantitative dataset led to the identification of 26 peptides, which are presented in lower abundance by HLA-B*27:06 and HLA-B*27:09 compared with disease-associated HLA-B27 subtypes. Although these differences were observed to be very subtle, these 26 peptides might encompass the sought-after arthritogenic peptide(s). PMID:26929215

  1. Microarray Analysis of Response of Salmonella during Infection of HLA-B27- Transfected Human Macrophage-Like U937 Cells

    Hinton Jay CD

    2010-07-01

    Full Text Available Abstract Background Human leukocyte antigen (HLA-B27 is strongly associated with the development of reactive arthritis (ReA in humans after salmonellosis. Human monocytic U937 cells transfected with HLA-B27 are less able to eliminate intracellular Salmonella enterica serovar Enteritidis than those transfected with control HLA antigens (e.g. HLA-A2. To investigate further the mechanisms by which HLA-B27-transfected cells allow increased replication of these bacteria, a DNA-based microarray was used for comparative genomic analysis of S. Enteritidis grown in HLA-B27- or HLA-A2-transfected cells. The microarray consisted of 5080 oligonucleotides from different serovars of Salmonella including S. Enteritidis PT4-specific genes. Bacterial RNA was isolated from the infected HLA-B27- or HLA-A2-transfected cells, reverse-transcribed to cDNA, and hybridized with the oligonucleotides on the microarrays. Some microarray results were confirmed by RT-PCR. Results When gene expression was compared between Salmonella grown in HLA-B27 cells and in HLA-A2 cells, 118 of the 4610 S. Enteritidis-related genes differed in expression at 8 h after infection, but no significant difference was detectable at 2 h after infection. These differentially expressed genes are mainly involved in Salmonella virulence, DNA replication, energy conversion and metabolism, and uptake and metabolism of nutrient substances, etc. The difference suggests HLA-B27-dependent modulation of Salmonella gene expression, resulting in increased Salmonella replication in HLA-B27-positive cells. Among the up-regulated genes were those located in Salmonella pathogenicity island (SPI-2, which play a central role in intracellular survival and replication of Salmonella. Conclusions This is the first report to show the regulation of Salmonella gene expression by HLA-B27 during infection of host cells. This regulation probably leads to increased Salmonella survival and replication in HLA-B27-positive

  2. Effect of HLA-B*27 and its subtypes on clinical manifestations and severity of ankylosing spondylitis in Iranian patients.

    Sasan Fallahi

    2013-12-01

    Full Text Available The aim of this study was to assess the role of HLA-B*27 and it's subtypes in determining severity and clinical manifestations of ankylosing spondylitis (AS.A total of 163 AS patients were assessed for clinical manifestations and severity using structured questionnaires. HLA-B*27 screening and B*27 sub-typing were performed by PCR.One hundred twenty two patients (74.8% were B*27 positive. The male to female ratio, peripheral arthritis, steroid use, intense dorsal kyphosis and decrease of cervical slope had a significantly higher frequency in B*27 positive patients compared to B*27 negative ones (p=0.01, 0.001, 0.01, 0.04 and 0.04, respectively. However, the age of diagnosis was significantly lower in B*27 positive patients (p=0.005. Trend in uveitis and some severity markers including: BASMI and ASQoL were toward higher values in B*27 positive group with no significant difference. After controlling confounding variables, significant relationship was found only between B*27 and BASMI (p=0.01. B*27 subtypes in patients were included B*2705: 48.4%, B*2702: 42.6%, B*2704: 5.7% and B*2707: 3.3%. No significant differences were seen for severity markers and clinical manifestations between subtypes; although trend toward lower values of severity markers, less intense dorsal kyphosis and less decrease of cervical slope were observed in B*2704 and B*2707 versus other polymorphisms.Clinical features and severity of AS is influenced by HLA-B*27. Trend toward higher severity markers in B*2705 and B*2702 versus other polymorphisms might be subject of interest for evaluation in other ethnicities with concentration to other novel susceptibility genes co-inherited in each B*27 subtype.

  3. Detection of HLA-B27 by flow cytometry and it's clinical evaluation: Analysis of 112 cases%流式细胞术检测HLA-B27及其临床意义(附112例分析)

    张臣青; 陈志哲

    2005-01-01

    目的通过流式细胞术检测外周血白细胞HLA-B27的表达,并探讨其对强直性脊柱炎(AS)的诊断价值.方法利用流式细胞仪(FCM)检测33例AS患者、34例背痛及腰腿痛患者及45例健康体检者的外周血HLA-B27表达.结果33例AS患者中,HLA-B27阳性30例(90.9%);34例背痛腰腿痛患者中,HLA-B27阳性4例(11.76%);45例健康人群中,HLA-B27阳性4例(8.9%).结论AS患者HLA-B27阳性率明显增高,HLA-B27检测可视为临床支持AS诊断的重要依据.

  4. Analysis of HLA-B15 and HLA-B27 in spondyloarthritis with peripheral and axial clinical patterns

    Londono, John; Santos, Ana Maria; Peña, Paola; Calvo, Enrique; Espinosa, Luis R; John D Reveille; Vargas-Alarcon, Gilberto; Jaramillo, Carlos A.; Valle-Oñate, Rafael; Avila, Mabel; Romero, Consuelo; Medina, Juan F.

    2015-01-01

    Objective Human leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns. Methods We studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were th...

  5. Endoplasmic reticulum aminopeptidase-1 alleles associated with increased risk of ankylosing spondylitis reduce HLA-B27 mediated presentation of multiple antigens.

    Seregin, Sergey S; Rastall, David P W; Evnouchidou, Irini; Aylsworth, Charles F; Quiroga, Dionisia; Kamal, Ram P; Godbehere-Roosa, Sarah; Blum, Christopher F; York, Ian A; Stratikos, Efstratios; Amalfitano, Andrea

    2013-12-01

    Ankylosing spondylitis (AS) is a chronic systemic arthritic disease that leads to significant disability and loss of quality of life in the ∼0.5% of the worldwide human population it affects. There is currently no cure for AS and mechanisms underlying its pathogenesis remain unclear. AS is highly genetic, with over 70% of the genetic risk being associated with the presence of HLA-B27 and endoplasmic reticulum aminopeptidase-1 (ERAP1) alleles. Furthermore, gene-gene interactions between HLA-B27 and ERAP1 AS risk alleles have recently been confirmed. Here, we demonstrate that various ERAP1 alleles can differentially mediate surface expression of antigens presented by HLA-B27 on human cells. Specifically, for all peptides tested, we found that an ERAP1 variant containing high AS risk SNPs reduced the amount of the peptide presented by HLA-B27, relative to low AS risk ERAP1 variants. These results were further validated using peptide catalysis assays in vitro, suggesting that high AS risk alleles have an enhanced catalytic activity that more rapidly destroys many HLA-B27-destined peptides, a result that correlated with decreased HLA-B27 presentation of the same peptides. These findings suggest that one mechanism underlying AS pathogenesis may involve an altered ability for AS patients harboring both HLA-B27 and high AS risk ERAP1 alleles to correctly display a variety of peptides to the adaptive arm of the immune system, potentially exposing such individuals to higher AS risk due to abnormal display of pathogen or self-derived peptides by the adaptive immune system. PMID:24028501

  6. HLA B27检测在强直性脊柱炎临床诊断中的意义

    黄翠珍; 蔡桂丰

    2005-01-01

    目的:评价 HLA B27检测在强直性脊柱炎 (AS)临床诊断中的作用.方法:应用磁珠酶联免疫检验试剂对怀疑患有 AS及其相关疾病的 265人作 HLA B27检测.采用 1984年的纽约修订的 AS诊断标准作为本研究的 AS诊断标准.结果:受检 265例中, HLA B27阳性检出率为 27.9%(74/265).高阳性率集中在轻壮年,并且男性阳性率 >女性阳性率(P< 0.01).按照纽约标准诊断为 AS的 69例患者中, HLA B27阳性率为 88.4%(61/69). HLA B27检测对诊断 AS的敏感度为 88.4%,特异度为 93.4%(183/196),诊断正确率为 92.1% (244/265).结论:对疑似 AS患者进行 HLA B27检测是必要的. HLA B27磁珠酶联免疫检验法对 AS诊断有高敏感性和高特异性,不失为当前 AS诊断的较好的实验指标.

  7. Concerted in vitro trimming of viral HLA-B27-restricted ligands by human ERAP1 and ERAP2 aminopeptidases.

    Elena Lorente

    Full Text Available In the classical human leukocyte antigen (HLA class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases and transported to the endoplasmic reticulum (ER lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. In this study, the possible cooperative effect of generating five naturally processed HLA-B27 ligands by both proteases was analyzed. We identified differences in the products obtained with increased detection of natural HLA-B27 ligands by comparing double versus single enzyme digestions by mass spectrometry analysis. These in vitro data suggest that each enzyme can use the degradation products of the other as a substrate for new N-terminal trimming, indicating concerted aminoproteolytic activity of ERAP 1 and ERAP2.

  8. Multiple sclerosis and HLA-B27 negative sacroiliitis in a Crohn’s disease patient

    K.H. Katsanos, N. Tzambouras, E.V. Tsianos

    2007-03-01

    Full Text Available SUMMARY A relationship between inflammatory bowel disease and MS is supported by a higher than expected coexistence of these diseases among families and individuals. A 32 year-old male with Crohn’s disease of the terminal ileum diagnosed 4 years earlier and HLA-B27 bilateral sacroiliitis diagnosed two years earlier, was admitted to our hospital because of an acute episode of blurred vision. In addition the patient complained of urine incontinence. Before this admission the patient had been elsewhere administered three doses of Remicade and 16mg of methylprednisolone p.os. During admission the diagnosis of multiple sclerosis was made (MRI and IgG Index and Remicade was discontinued. The patient was started on therapy with interferon-beta for MS, oxybutynin hydrochloride (10mg/day for urine incontinence, prednizolone (10mg/day, methotrexate (10mg/week and azathioprine (100mg/day for Crohn’s disease and is now in excellent clinical status. To the best of our knowledge this is one of the very rare cases of Crohn’s disease with HLA-B27 negative sacroiliitis preceding multiple sclerosis diagnosis. Key words: Crohn’s disease, inflammatory bowel disease, ulcerative colitis, multiple sclerosis, Remicade

  9. Combined effects of ankylosing spondylitis-associated ERAP1 polymorphisms outside the catalytic and peptide-binding sites on the processing of natural HLA-B27 ligands.

    Martín-Esteban, Adrian; Gómez-Molina, Patricia; Sanz-Bravo, Alejandro; López de Castro, José A

    2014-02-14

    ERAP1 polymorphism involving residues 528 and 575/725 is associated with ankylosing spondylitis among HLA-B27-positive individuals. We used four recombinant variants to address the combined effects of the K528R and D575N polymorphism on the processing of HLA-B27 ligands. The hydrolysis of a fluorogenic substrate, Arg-528/Asp-575 ERAP1 was a major determinant of the abundance of these peptides in vivo. The hydrolysis of fluorogenic and peptide substrates by an HLA-B27 ligand or a shorter peptide, respectively, was increasingly inhibited as a function of ERAP1 activity, indicating that residues 528 and 575 affect substrate inhibition of ERAP1 trimming. The significant and complex effects of co-occurring ERAP1 polymorphisms on multiple HLA-B27 ligands, and their potential to alter the immunological and pathogenetic features of HLA-B27 as a function of the ERAP1 context, explain the epistatic association of both molecules in ankylosing spondylitis. PMID:24352655

  10. The Method for Detecting HLA-B27 by Flow Cytometer and Its Application Study about Acute Anterior Uveitis%流式细胞术检测HLA-B27及其在急性前葡萄膜炎诊治中的应用研究

    张新颖; 宋玉国; 石萍; 刘祥龙

    2009-01-01

    目的:建立流式细胞仪检测白细胞膜HLA-B27检测方法.研究急性前葡萄膜炎(AAU)患者外周血白细胞HLA-B27表达情况,比较AAU患者和正常人HLA-B27阳性率的差异性;研究HLA-B27阳性AAU病例合并强直性脊柱炎(AS)的发生率,和AAU复发情况,为临床诊断和治疗提供科学依据.方法:用异硫氰酸荧光素(FITC)标记HLA-B27单克隆抗体,对细胞膜表面HLA-B27抗原进行标记,然后用流式细胞仪检测HLA-B27阳性细胞.检测方法建立后,进行临床应用研究.按临床诊断标准,确定AAU研究病例,并进行合并AS的临床诊断,记录治疗后AAU复发情况.对各组病例分别检测HLA-B27,研究各组的差异性.结果:共检测分析了47例AAU病例,其中HLA-B27阳性病例30例,阳性率为63.83%.明显高于正常对照组(P<0.05).47例AAU病人中,合并AS的有18例,这18例中HLA-B27阳性率高达72.22%,明显高于单纯AAU病例的HLA-B27阳性率(41.38%)(P<0.05).30例HLA-B27阳性AAU病例中有25例被观察到复发情况,复发率为83.33%,明显高于HLA-B27阴性AAu病例的复发率(47.06%,8/17)(P<0.05).结论:检测HLA-B27有助于AAU的诊断,是一项有效的辅助诊断指标.对于HLA-B27阳性的AAU病例,要注意AS的合并发生,提高相关疾病的诊断水平.对于HLA-B27阳性病例,注意疾病的复发情况,发现复发及时就医治疗,以减少并发症的发生减缓病情进展.

  11. Analysis of the diagnostic significance of HLA-B27 in spondyloarthropathy and non-spondyloarthropathy: report of 4 817 cases%4817例HLA-B27检测对SpA和非SpA诊断价值的分析

    魏秋静; 李秋霞; 李齐光

    2011-01-01

    Objective: To study the application of HLA-B27 antigen detection in diagnosis of spondyloarthropathy (SpAs) in patients with low back pain.Methods: HLA-B27 antigen detection with complement-dependent lymphocytotoxicity was performed in 4414 patients who sought medical consultation with low back pain and 403 healthy controls.Analysis of HLA-B27 positive distributions in different gender and diseases ( SpA and have non-SpA) was performed.Results: The positive rate of HLA-B27 antigen was 49.81% in 4 414 patients with low back pain, while no significant difference revealed between genders (P > 0.05 ).Positive rates of HLA-B27 in patients with ankylosing spondylitis ( AS) , undifferentiated spondyloarthropathy (USpA) , Juvenile spondyloarthropathy (JSpAs), reactive arthritis (ReA), psoriatic arthritis (PsA) and non-SpAs were 90.07%, 28.85%, 68.81%, 52.94%, 67.74% and 19.33%, respectively, with significant differences with the healthy control group (P < 0.05).Conclusions: Positive HLA-B27 detection can be found in patients with non-SpAs, suggesting that HLA-B27 is not an independent diagnostic factor of SpA.%目的:探讨HLA-B27对腰背痛疑诊或待排除SpA患者的鉴别诊断价值.方法:采用补体依赖淋巴细胞毒试验(CDC)检测4 414例以腰背痛就诊的患者及403名健康对照者的HLA-B27,结合患者临床资料分析HLA-B27在不同性别和疾病(SpA和非SpA两组)中的阳性分布情况.结果:4 414例腰背痛疑诊或待排除SpA人群HLA-B27的阳性率为49.81%,男女HLA-B27阳性率比较差异无统计学意义(P>0.05);在SpA组AS、未分化型SpA(USpA)、幼年SpA(JSpA)、反应性关节炎(ReA)和银屑病关节炎(PsA) HLA-B27阳性率分别为90.07%、28.85%、68.81%、52.94%和67.74%.非SpA组HLA-B27阳性率为19.33%,与健康对照组比较差异有统计学意义(P<0.05).结论:非SpA患者HLA-B27也可能阳性,HLA-B27检测阳性不能单纯考虑SpA.

  12. 379例疑似强直性脊柱炎患者HLA-B27抗原检查结果分析

    孙维萍

    2007-01-01

    目的:本文是为了总结本地区强直性脊柱炎与HLA-B27抗原的相关情况.方法:我们采用的是淋巴细胞毒实验Teraski血清盘法.结果:379例疑似强直性脊柱炎患者的HLA-B27抗原检查阳性的有124例,阴性为255例.结论:本地区强直性脊柱炎与HLA-B27抗原有极强相关.

  13. The Application of HLA-B27 Detection in the Clinical Diagnosis of Ankylosing Spondylitis%HLA-B27检测在强直性脊柱炎临床诊断中的应用(附120例报告)

    章祖成; 施水潮; 钱海平; 严力生

    2002-01-01

    目的:评价HLA-B27检测在强直性脊柱炎(AS)临床诊断中的作用.方法:对怀疑患有AS及其相关疾病的120人作HLA-B27检测,采用纽约标准改良的AS诊断标准作为本研究的AS诊断标准.结果:本组受检120例中,HLA-B27(+)56例,占受检总数的46.67%,按本研究改良标准诊断为AS 53例, 其中HLA-B27(+)48例.本组16周岁以下13例受检者,HLA-B27(+)7例均符合JAS诊断标准.结论:HLA-B27检测对提高AS的诊断率和对轻型、早期AS病例的发现具有临床诊断价值.

  14. The clinical value of HLA-B27/B7 in the diagnosis of ankylosing spondysis%HLA-B27/B7抗原检测在诊断强直性脊柱炎中的临床价值

    罗玲; 严海燕; 罗晓红

    2013-01-01

    目的 探讨HLA-B27/B7抗原检测在诊断强直性脊柱炎(AS)中的临床价值.方法 选取144例门诊及住院高度疑似AS的患者,应用流式细胞仪对其标本进行HLA-B27/B7抗原检测.结果 HLA-B27抗原阳性率在青少年人群比较高,且男性显著高于女性,受检的144例患者,HLA-B27抗原阳性率为63.9%,低于确诊为AS的阳性率(91.1%).HLA-B27抗原检测对诊断AS的灵敏度为91.1%(82/90),特异度为81.5%(44/54),正确率为87.5%(126/144).结论 HLA-B27抗原与AS密切相关,对临床诊断AS很有帮助,用流式细胞术进行检测是较好的方法.

  15. Peptide handling by HLA-B27 subtypes influences their biological behavior, association with ankylosing spondylitis and susceptibility to endoplasmic reticulum aminopeptidase 1 (ERAP1).

    García-Medel, Noel; Sanz-Bravo, Alejandro; Alvarez-Navarro, Carlos; Gómez-Molina, Patricia; Barnea, Eilon; Marcilla, Miguel; Admon, Arie; de Castro, José A López

    2014-12-01

    HLA-B27 is strongly associated with ankylosing spondylitis (AS). We analyzed the relationship between structure, peptide specificity, folding, and stability of the seven major HLA-B27 subtypes to determine the role of their constitutive peptidomes in the pathogenicity of this molecule. Identification of large numbers of ligands allowed us to define the differences among subtype-bound peptidomes and to elucidate the peptide features associated with AS and molecular stability. The peptides identified only in AS-associated or high thermostability subtypes with identical A and B pockets were longer and had bulkier and more diverse C-terminal residues than those found only among non-AS-associated/lower-thermostability subtypes. Peptides sequenced from all AS-associated subtypes and not from non-AS-associated ones, thus strictly correlating with disease, were very rare. Residue 116 was critical in determining peptide binding, thermodynamic properties, and folding, thus emerging as a key feature that unified HLA-B27 biology. HLA-B27 ligands were better suited to TAP transport than their N-terminal precursors, and AS-associated subtype ligands were better than those from non-AS-associated subtypes, suggesting a particular capacity of AS-associated subtypes to bind epitopes directly produced in the cytosol. Peptides identified only from AS-associated/high-thermostability subtypes showed a higher frequency of ERAP1-resistant N-terminal residues than ligands found only in non-AS-associated/low-thermostability subtypes, reflecting a more pronounced effect of ERAP1 on the former group. Our results reveal the basis for the relationship between peptide specificity and other features of HLA-B27, provide a unified view of HLA-B27 biology and pathogenicity, and suggest a larger influence of ERAP1 polymorphism on AS-associated than non-AS-associated subtypes. PMID:25187574

  16. Increase of HLA-DRB1*0408 and -DQB1*0301 in HLA-B27 positive reactive arthritis

    Tuokko, J; Reijonen, H.; Ilonen, J; K. Anttila; Nikkari, S; Mottonen, T; Yli-Kerttula, U; Toivanen, A

    1997-01-01

    OBJECTIVE—To study HLA class II association in reactive arthritis.
METHODS—63 patients with reactive arth-ritis and 46 with rheumatoid arthritis were included in the study. HLA-DR alleles were determined by using a sequence specific PCR method. Oligonucleotide hybridisation was used for definition of DRB1*04 subtypes and DQB1 alleles. HLA-B27 was determined by standard microcytotoxity test or by PCR. HLA-B27 subtyping was made by sequencing.
RESULTS—46 (73%) of 63 patients with reactive arthr...

  17. 强直性脊柱炎患者血液HLA-B27的临床参考值的预测%The Predicted Clinical Reference Value of HLA-B27 in the Peripheral Venous Blood of Ankylosing Spondylitis Patients

    张金飞

    2012-01-01

    目的 以实时荧光定量PCR(FQ-PCR)检测可疑患者HLA-B27的定量水平,研究强直性脊柱炎(AS)与HLA-B27的相关性,明确HLA-B27的检测值范围并用于AS的确诊诊断.方法 针对本院2005年~2010年收集的168例骶髂关节及下腰部疼痛等症状疑似AS病例进行回顾性分析,获得所有病例外周静脉血标本,然后通过实时荧光定量PCR进行HLA-B27的定量检测,疑似病例分为AS患者、HLA-B27阳性的非AS患者、HLA-B27阴性的非AS患者三组,根据临床体征、影像学进行确诊病情,同时选取健康体检者52例外周静脉血标本的HLA B-27测定结果进行对照,统计分析各变量与AS存在之间的关系.结果 AS患者、HLA-B27阳性的非AS患者、HLA-B27阴性的非AS患者、健康体检者的HLA-B27循环阈值(ct)平均值分别为:26.3 copies/ml、17.5 copies/ml、6.2 copies/ml、4.9 copies/ml,单变量分析表明,HLA-B27与化脓性关节炎明显相关(P<0.05).结论 AS患者HLA-B27定量分析循环阈值(ct)的95%参考值范围为(17.3~35.3)copies/ml,HLA-B27定量分析可作为疾病发病的参照影响因素及预测因素.%A fhuorogenic quantitative polymerase chain reaction( FQ-PCR) was used to detect quantitative level of the suspicious ankylosing spondylitis patients, to detennine the relativity between ankylosing spondylitis and HLA-B27, and the predicted reference value got from this experiment was used to diagnose ankylosing spondylitia. Methods 168 suspicous ankylosing spondylitia cases with the pain of sacroiliac joints and lower waist collected from 2002 to 2010, was to do retrospective analysis, all the blood specimen was got to analyze the quantitative level of HLA-B27. All patients on the basis of clinic and this experiment were divided into 3 groups; AS patients, non-AS patients with HLA-B27-positive patients group, non-AS patients with HLA-B27-negative patients group. 52 cases were collected as control group. Statistical analysis was to analyze the

  18. 内蒙古地区疑似强直性脊柱炎患者HLA-B27抗原阳性率观察%Investigation of positive rate of HLA-B27 antigen in patients with suspected ankylosing spondylitis in Inner Mongolia

    托娅; 张军力

    2013-01-01

    Objective To investigate the relationship between suspected ankylosing spondylitis and HLA-B27 antigen in Inner Mongolia by detecting the positive rate and expression intensity of HLA-B27 antigen in 998 suspected AS patients, and evaluate its clinical significance. Methods The positive rate and the mean fluorescence intensity (MFI) of HLA-B27 antigen on the peripheral blood T lymphocytic detected by flow cytometer. Results Among the 998 suspected AS patients, the majority patients (77.35%) were aged from 21 to 50 years old, and the ratio between male and female was 1.4∶1. Among the all patients, the positive rate of antigen HLA-B27 was 28.86%, and the male and female patients' positive rates of HLA-B27 antigen were 33.05% and 23.02%, respectively (P<0.05). The MFI of male and female patients were significantly different (P<0.05). Conclusion The patients with AS in Inner Mongolia are strongly associated with HLA-B27 antigen. Detection of HLA-B27 antigen expression intensity in suspected AS patients with FCM is helpful to diagnosis and differential diagnosis of AS.%目的通过检测998例疑似强直性脊柱炎(Ankylosing spondylitis,AS)患者HLA-B27抗原阳性率和表达强度,了解内蒙古地区AS与HLA-B27抗原的相关性,并初步探讨其临床意义。方法采用流式细胞术检测患者外周血T淋巴细胞膜上的HLA-B27抗原和其平均荧光强度(mean fluorescence intensity,MFI)。结果998例疑似AS患者以21~50岁青壮年为主,占77.35%;男女比例为1.4∶1;998例疑似AS患者的HLA-B27抗原阳性率28.86%;男女患者HLA-B27抗原阳性率分别为33.05%和23.02%(P<0.05);男女阳性患者的MFI有明显差异(P<0.05)。结论内蒙古地区AS患者与HLA-B27抗原有着很强的相关性。采用流式细胞技术检测临床疑似AS患者T淋巴细胞HLA-B27表达强度有助于诊断和鉴别诊断AS。

  19. Complete sequence of HLA-B27 cDNA identified through the characterization of structural markers unique to the HLA-A, -B, and -C allelic series

    Szoets, H.; Reithmueller, G.; Weiss, E.; Meo, T.

    1986-03-01

    Antigen HLA-B27 is a high-risk genetic factor with respect to a group of rheumatoid disorders, especially ankylosing spondylitis. A cDNA library was constructed from an autozygous B-cell line expressing HLA-B27, HLA-Cw1, and the previously cloned HLA-A2 antigen. Clones detected with an HLA probe were isolated and sorted into homology groups by differential hybridization and restriction maps. Nucleotide sequencing allowed the unambiguous assignment of cDNAs to HLA-A, -B, and -C loci. The HLA-B27 mRNA has the structure features and the codon variability typical of an HLA class I transcript but it specifies two uncommon amino acid replacements: a cysteine in position 67 and a serine in position 131. The latter substitution may have functional consequences, because it occurs in a conserved region and at a position invariably occupied by a species-specific arginine in humans and lysine in mice. The availability of the complete sequence of HLA-B27 and of the partial sequence of HLA-Cw1 allows the recognition of locus-specific sequence markers, particularly, but not exclusively, in the transmembrane and cytoplasmic domains.

  20. Application of PCR-SBT method in HLA-B27 detection in AS patients%聚合酶链反应-直接测序法在强直性脊柱炎患者 HLA-B27检测中的应用

    王平均; 孙灵迪; 梅传忠; 武晓茜; 邵先安

    2015-01-01

    目的:探讨聚合酶链反应-直接测序法(polymerase chain reaction sequence-based typing,PCR-SBT)检测人类白细胞抗原 B27(human leukocyte antigen B27,HLA-B27)在强直性脊柱炎(ankylosing spondylitis,AS)临床诊断中的价值。方法应用 PCR-SBT 法和临床常用的 IMS-ELISA 法对120例疑似 AS 患者外周血进行 HLA-B27检测。以 SPSS17.0软件的配对χ2检验和受试者工作特征曲线下面积对两种方法检测 HLA-B27在 AS 诊断中的价值进行评价。结果120例疑似 AS 患者中,PCR-SBT 和 IMS-ELISA 法 HLA-B27检测阳性率分别为45.83%(55/120),37.50%(45/120)。两种方法检测 HLA-B27有统计学差异(P=0.031)。PCR-SBT 法敏感度和特异度分别为96.36%,96.92%;IMS-ELISA 法的敏感度和特异度分别为69.09%,89.23%。两者的 AUC 分别为0.966和0.792。结论与传统的 IMS-ELISA 法相比,在 AS 的临床诊断中 PCR-SBT 法检测 HLA-B27的敏感度和特异度更高,方法更优。%Objective The aim of this study was to compare PCR-SBT to IMS-ELISA in the HLA-B27 detection in the ankylosing spondylitis (AS)patients.Methods Simultaneously,PCR-SBT and IMS-ELISA were used to detect the HLA-B27 expression in peripheral blood samples which were suspected patients with AS from 120 cases.Chi square test of paired design and the area under curve of receiver operating characteristics of SPSS17.0 software were used to e-valuate the value of PCR-SBT and IMS-ELISA in HLA-B27 detection of AS patients.Results Among 120 cases of sus-pected patients with AS,the positive rates of HLA-B27 detected by PCR-SBT and IMS-ELISA were 45.83% (55/120),37.50%(45/120),respectively.There was statistical difference between the two methods in the HLA-B27 detec-tion (P =0.032).The sensibility and specificity of PCR-SBT were 96.36%,96.92%,respectively;while the sensibility and the specificity of IMS-ELISA were 69.09%,89.23%,respectively

  1. The HLA-B27,B7,B13 and B40 Antigen Expression of the Ankylosing Spondylitis and the Analysis of the Immunology Index%强直性脊柱炎患者HLA-B27、B7、B13、B40抗原表达及免疫学指标的分析

    李士军; 袁宏; 王滨; 曹华军

    2005-01-01

    目的探讨强直性脊柱炎患者HLA-B27、B7、B13、B40的抗原表达,发现抗原相互杂合与交叉反应,以及强直性脊柱炎患者的免疫学指标的变化.方法采用NIH微量淋巴细胞毒法对HLA-B27等抗原进行检测,抗核抗体采用间接免疫荧光法,免疫球蛋白及补体均采用免疫速率散射法测定.结果126例初诊患者中HLA-B27阳性率为34.1%,HLA-B7、B13、B40的阳性率分别为6.3%,13.5%,11.1%.HLA-B27阳性组中HLA-B13阳性率为27.9%,HLA-B40阳性率为23.3%,分别高于HLA-B27阴性组(6.0%,4.8%),而HLA-B7的阳性率两组无显著性差异.HLA-B27阳性组的免疫球蛋白、补体、抗核抗体指标均显著高于HLA-B27阴性组(P均<0.05).结论检测强直性脊柱炎患者HLA-B27及相关B抗原有助于疾病诊断和抗原交叉反应的分析,体液免疫异常及自身抗体的出现与HLA-B27密切相关.

  2. Association of IL1R polymorphism with HLA-B27 positive in Iranian patients with ankylosing spondylitis.

    Mahmoudi, M; Amirzargar, A A; Jamshidi, A R; Farhadi, E; Noori, S; Avraee, M; Nazari, B; Nicknam, M H

    2011-12-01

    Ankylosing spondylitis (AS) is one of the most common causes of inflammatory arthritis, with an estimated prevalence of 0.1-0.9%. Genetic factors have been strongly implicated in its aetiology, and heritability as assessed by twin studies has been estimated to be >90%. HLA- B27 is almost essential for inheritance of AS; it is not merely sufficient for explaining the pattern of familial recurrence of the disease. This study's purpose is to investigate the association of ankylosing spondylitis with single-nucleotide polymorphisms (SNPs) in the IL-1 family: IL-1a (-889C/T) rs1800587, IL-1b (-511C/T) rs16944, IL-1b (+3962C/T) rs1143634, IL-1R (Pst-1 1970C/T) rs2234650 and IL-1RA (Mspa-1 11100C/T) rs315952. 99 unrelated Iranian AS patients and 217 healthy control subjects were selected. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. The allele and genotype frequencies of the polymorphisms were determined: The IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with AS. Genotype frequencies at IL1R rs2234650 differed between cases and controls (χ(2)=8.85; p=0.01); the IL1R rs2234650 C/T and T/T genotypes were less common in AS patients than controls. The IL1R rs2234650 C/T genotype was inversely associated with AS comparing with the IL1R rs2234650 C/C genotype (OR=0.48; p=0.005). IL1R rs2234650 C/T genotype was less common in patients than controls (OR=0.37; p=0.02).Furthermore IL1R rs2234650 T allele was strongly associated with HLA-B2702 patients rather than HLA-B2705 but was not associated with HLA-B27 negative patients (OR=0.33; p=0.01). Polymorphisms of IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with ankylosing spondylitis but inversely in this study IL1R rs2234650 was significantly associated and carriage of T allele in IL1R rs2234650 seems to be protective, while carriage of C allele result in two fold higher risk of developing AS. PMID

  3. The correlation analysis of HLA-B27 in the diagnosis of ankylosing spondyfitis%人类白细胞抗原-B27与强直性脊柱炎的相关性分析

    朱振军; 程田; 李碧波

    2010-01-01

    目的 探讨人类白细胞抗原-B27(HLA-B27)检测在强直性脊柱炎(AS)早期诊断中的临床价值.方法 使用序列特异性引物-聚合酶链式反应(PCR-SSP)法对500例健康体检者(非AS对照组)、360例AS疑似患者(AS疑似组)和100例AS患者(AS组) 进行HLA-B27抗原检测.结果 非AS对照组、AS疑似组和AS组的HLA-B27阳性率分别为3.3%、 48.9%和92.5%,AS组、AS疑似组的HLA-B27阳性率明显高于非AS对照组(P<0.01),AS组的HLA-B27阳性率明显高于AS疑似组(P<0.01).结论 HLA-B27抗原与AS疾病相关,检测HLA-B27抗原对疑似AS患者的早期诊断有重要意义.%Objective To explore the clinical value of HLA-B27 in patients with ankylosing spondyfitis. Methods Using PCR-SSP to detect the HLA-B27 of 500 healthy people (non-AS group),360 presumed AS patients (suspectable group) and 100 AS patients(AS group). Results The positive rates of HLA-B27 of non-AS group, suspectable group, AS group were 3.3%,48.9% and 92.5%, respectively. The positive rate of HLA-B27 of AS group and suspectable group was obviously higher than that in non-AS group (P<0.05). The positive rate of HLA-B27 of AS group was obviously higher than that in suspectable group (P<0.05). Conclusions There is positive correlation between AS and HLA-B27.It is very important for the early diagnosis of AS.

  4. Sulfasalazine Treatment Suppresses the Formation of HLA-B27 Heavy Chain Homodimer in Patients with Ankylosing Spondylitis

    Hui-Chun Yu

    2015-12-01

    Full Text Available Human leukocytic antigen-B27 heavy chain (HLA-B27 HC has the tendency to fold slowly, in turn gradually forming a homodimer, (B27-HC2 via a disulfide linkage to activate killer cells and T-helper 17 cells and inducing endoplasmic reticulum (ER stress to trigger the IL-23/IL-17 axis for pro-inflammatory reactions. All these consequences lead to the pathogenesis of ankylosing spondylitis (AS. Sulfasalazine (SSA is a common medication used for treatment of patients with AS. However, the effects of SSA treatment on (B27-HC2 formation and on suppression of IL-23/IL-17 axis of AS patients remain to be determined. In the current study, we examine the (B27-HC2 of peripheral blood mononuclear cells (PBMC, the mean grade of sarcoiliitis and lumbar spine Bath Ankylosing Spondylitis Radiology Index (BASRI scores of 23 AS patients. The results indicated that AS patients without (B27-HC2 on PBMC showed the lower levels of mean grade of sarcoiliitis and the lumbar spine BASRI scores. In addition, after treatment with SSA for four months, the levels of (B27-HC2 on PBMCs were significantly reduced. Cytokines mRNA levels, including TNFα, IL-17A, IL-17F and IFNγ, were also significantly down-regulated in PBMCs. However, SSA treatment did not affect the levels of IL-23 and IL-23R mRNAs.

  5. Sulfasalazine Treatment Suppresses the Formation of HLA-B27 Heavy Chain Homodimer in Patients with Ankylosing Spondylitis.

    Yu, Hui-Chun; Lu, Ming-Chi; Huang, Kuang-Yung; Huang, Hsien-Lu; Liu, Su-Qin; Huang, Hsien-Bin; Lai, Ning-Sheng

    2016-01-01

    Human leukocytic antigen-B27 heavy chain (HLA-B27 HC) has the tendency to fold slowly, in turn gradually forming a homodimer, (B27-HC)₂ via a disulfide linkage to activate killer cells and T-helper 17 cells and inducing endoplasmic reticulum (ER) stress to trigger the IL-23/IL-17 axis for pro-inflammatory reactions. All these consequences lead to the pathogenesis of ankylosing spondylitis (AS). Sulfasalazine (SSA) is a common medication used for treatment of patients with AS. However, the effects of SSA treatment on (B27-HC)₂ formation and on suppression of IL-23/IL-17 axis of AS patients remain to be determined. In the current study, we examine the (B27-HC)₂ of peripheral blood mononuclear cells (PBMC), the mean grade of sarcoiliitis and lumbar spine Bath Ankylosing Spondylitis Radiology Index (BASRI) scores of 23 AS patients. The results indicated that AS patients without (B27-HC)₂ on PBMC showed the lower levels of mean grade of sarcoiliitis and the lumbar spine BASRI scores. In addition, after treatment with SSA for four months, the levels of (B27-HC)₂ on PBMCs were significantly reduced. Cytokines mRNA levels, including TNFα, IL-17A, IL-17F and IFNγ, were also significantly down-regulated in PBMCs. However, SSA treatment did not affect the levels of IL-23 and IL-23R mRNAs. PMID:26729099

  6. KIR3DL1 interaction with HLA-B27 is altered by ankylosing spondylitis associated ERAP1 and enhanced by MHC class I cross-linking.

    Abdullah, Hasan; Zhang, Zhenbo; Yee, Kirby; Haroon, Nigil

    2015-01-01

    Ankylosing spondylitis (AS) is a chronic, inflammatory arthritis of the spine and peripheral joints linked to the antigen presenting molecule HLA-B27. The risk of AS is increased in patients possessing endoplasmic reticulum aminopeptidase-1 (ERAP1) polymorphisms rs30187 and rs27044 encoding amino acid changes K528R and Q730E, respectively. Dysfunction of ERAP1 is hypothesized to cause changes in expression of HLA-B27 classical (pHLA) and non-classical (FHC) conformers on antigen presenting cells (APCs), which interact with the natural killer (NK) cell receptor KIR3DL1. Dysregulation of this pathway may be pathogenic in AS. APC cell lines expressing HLA-B27 were found to inhibit cytokine production in KIR3DL1+ NK cells due to decreased APC-NK cell adhesion, and possibly activation of receptor down-regulation. Blocking pHLA and FHC reveals that both conformers inhibit cytokine production through KIR3DL1. KIR3DL1 affinity and HLA-B27 surface expression studies suggest that ERAP1 R528 and E730 expression protects from AS by generating sub-optimal pHLA, causing reduced KIR3DL1 affinity and weaker cytokine inhibition. Secondarily we observed that KIR3DL1 binding to C1R-B27 APCs is enhanced by blocking pHLA, but not FHC, raising the possibility that antibody mediated HLA-B27 cross-linking may be important in enhancing KIR3DL1+ NK cell function. This study establishes the role of both FHC and pHLA in modulating NK cell cytokine secretion and adhesion functions by interacting with KIR3DL1. This interaction varies depending on the AS association status of the ERAP1 variant expressed in APCs. Additionally antibody cross-linking of HLA-B27 enhances KIR3DL1 binding and as such could be an important pathogenic mechanism in AS. PMID:26321090

  7. 强直性脊柱炎患者HLA-B27、B7、B13和B40的检测及其与临床相关性的研究

    潘静芳; 黄瑛

    2005-01-01

    目的探讨湖北省强直性脊柱炎 (AS)患者 HLA- B27、 B7、 B13和 B40的抗原表达情况及其临床诊断意义.方法采用微量淋巴细胞毒法检测 179例 AS患者 HLA- B27、 B7、 B13和 B40的抗原表达情况,并分析其与临床的相关性.结果 HLA- B27、 B7、 B13和 B40的抗原阳性率分别为 74.9%、 11.7%、 14.0%和 13.4%.HLA- B27阳性的 AS患者多以外周关节受累为主要症状,其平均发病年龄比 HLA- B27阴性的 AS患者小; HLA- B27阴性的 AS患者多以腰痛为主要症状,其平均发病年龄较大.结论 HLA- B27阳性对以外周关节受累为首发症状且年龄在 25岁以下的 AS患者诊断意义较大.

  8. Association between HLA-B27 antigen and acute anterior uveitis%人类白细胞抗原与急性前葡萄膜炎的相关性

    杜红艳; 杜鹏程

    2009-01-01

    目的:探讨急性前葡萄膜炎(acute anterior uveitis,AAU)与人类白细胞抗原(human leucolyte antigen,HLA-B27)的相关性.方法:应用聚合酶链反应(sequence special prime polymerase chain reaction,SSP-PCR)基因检测技术,对AAU患者进行HLA-B27基因检测,观察HLA-B27阳性与阴性AAU临床特征并加以分析.结果:在36例AAU患者中,HLA-B27抗原阳性29例,阳性率81%,37例健康对照组,阳性9例,阳性率24%,两者有显著性差异(χ2=23.12,P<0.01).结论:HLA-B27与AAU明显相关,HLA-B27阳性与阴性患者有一定程度的差异,常伴有全身脊柱关节病,采用SSP-PCR基因检测技术测定HLA-B27快速、简单、准确性高、客观性强,值得推广应用.

  9. Türk ankilozan spondilitli hastalarda HLA-B27 ve MEFV gen mutasyonları arasındaki ilişki

    SARIKAYA PEKACAR, Filiz

    2015-01-01

    Ankilozan spondilit (AS), patogenezinde bir çok genetik, immunolojik ve çevresel faktörün birlikte rol oynadığı  inflamatuvar bir hastalıktır. Genetik faktörler arasında en büyük pay HLA -B27’nindir. Genom  çapında ilişkilendirme çalışmaları sonucu AS ile ilgili bir çok gen bulunmuş MHC dışı genlerin hastalığın  gelişiminde rol oynadığı düşünülmüştür.
    Bu tez çalışmasında HLA-B27, MEFV gen mutasyonları, IL12B, IL23R ve ERAP1 gen polimorfiz...

  10. HLA-B27检测在强直性脊柱炎诊断中的临床价值探讨

    刘晖

    2010-01-01

    目的探讨HLA—B27检测在强直性脊柱炎(AS)诊断中的临床价值。方法选择我院确诊的AS患者83例作为观察组,随机抽取在我院健康体检人群80例做为对照组,进行HLA~B27检测。结果观察组HLA—B27阳性率明显高于健康对照组,差异有统计学意义(P〈0.01)。结论HLA-B27与AS具有很强的相关性,检测HLA-B27可明显提高诊断特异性。

  11. Loss of viral fitness and cross-recognition by CD8+ T cells limit HCV escape from a protective HLA-B27–restricted human immune response

    Dazert, Eva; Neumann-Haefelin, Christoph; Bressanelli, Stéphane; Fitzmaurice, Karen; Kort, Julia; Timm, Jörg; McKiernan, Susan; Kelleher, Dermot; Gruener, Norbert; Tavis, John E.; Rosen, Hugo R.; Shaw, Jaqueline; Bowness, Paul; Blum, Hubert E.; Klenerman, Paul

    2009-01-01

    There is an association between expression of the MHC class I molecule HLA-B27 and protection following human infection with either HIV or HCV. In both cases, protection has been linked to HLA-B27 presentation of a single immunodominant viral peptide epitope to CD8+ T cells. If HIV mutates the HLA-B27–binding anchor of this epitope to escape the protective immune response, the result is a less-fit virus that requires additional compensatory clustered mutations. Here, we sought to determine wh...

  12. AIDS-protective HLA-B*27/B*57 and chimpanzee MHC class I molecules target analogous conserved areas of HIV-1/SIVcpz

    de Groot, Natasja G.; Corrine M C Heijmans; Zoet, Yvonne M.; de Ru, Arnoud H.; Verreck, Frank A.; van Veelen, Peter A.; Drijfhout, Jan W; Doxiadis, Gaby G M; Remarque, Edmond J.; Doxiadis, Ilias I. N.; van Rood, Jon J.; Koning, Frits; Bontrop, Ronald E

    2010-01-01

    In the absence of treatment, most HIV-1-infected humans develop AIDS. However, a minority are long-term nonprogressors, and resistance is associated with the presence of particular HLA-B*27/B*57 molecules. In contrast, most HIV-1-infected chimpanzees do not contract AIDS. In comparison with humans, chimpanzees experienced an ancient selective sweep affecting the MHC class I repertoire. We have determined the peptide-binding properties of frequent chimpanzee MHC class I molecules, and show tha...

  13. Genetic Polymorphisms of Stromal Interaction Molecule 1 Associated with the Erythrocyte Sedimentation Rate and C-Reactive Protein in HLA-B27 Positive Ankylosing Spondylitis Patients

    Wei, James Cheng-Chung; Hung, Kuo-Sheng; Hsu, Yu-Wen; Wong, Ruey-Hong; Huang, Chun-Huang; Jan, Ming-Shiou; Wu, Shyh-Jong; Juan, Yung-Shun; Chang, Wei-Chiao

    2012-01-01

    Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The development of ankylosing spondylitis is still unclear. Genetics factors such as human leukocyte antigen HLA-B27 and ERAP1 have been widely reported to associate to AS susceptibility. In this study, we enrolled 361 AS patients and selected four tagging single nucleotides polymorphisms (tSNPs) at STIM1 gene. The correlation between STIM1 genetic polymorphisms and AS activity index (...

  14. The Rate of Helicobacter pylori Seropositivity in a Group of Korean Patients with HLA-B27-Associated Acute Anterior Uveitis

    Jeong Hun Bae; Joon Mo Kim

    2015-01-01

    Purpose To investigate an association between Helicobacter pylori seropositivity and HLA-B27-positive acute anterior uveitis (AAU) in Korean patients. Methods Retrospective analysis was performed with data from 106 patients previously diagnosed with AAU without clinical evidence of spondyloarthropathy. Serum immunoglobulin G antibodies to H. pylori were measured by enzyme-linked immunosorbent assay, and HLA typing was performed using polymerase chain reaction of DNA amplification. We included...

  15. Doğu Anadolu Bölgesinde Ankilozan Spondilitli Hastalarda HLA B27 Frekansının Dağılımı

    Diyarbakır, Eda; Eyerci, Nilnur; UZKESER, Hülya; Karatay, Saliha; Topçu, Atilla; Yıldırım, Kadir; Pirim, İbrahim

    2012-01-01

    Ankilozan spondilit (AS) etyolojisi bilinmeyen kronik enflamatuvar bir hastalıktır. Patogenezde genetik ve çevresel faktörlerin önemli rol oynadığı bilinmektedir. AS gelişimi ile HLA B27 arasında güçlü bir birliktelik saptanmıştır. Bu çalışma ile daha önceki literatür bilgileri ışığında bölgemizdeki HLA B27-AS ilişkisi karşılaştırıldı. Bu çalışmada, modifiye New York kritelerine göre sınıflandırılmış AS'li hasta ve sağlıklı kontroller üzerinde HLA B27 frekansı araştırılmıştır. Çalışmaya b...

  16. A computational docking study on the pH dependence of peptide binding to HLA-B27 sub-types differentially associated with ankylosing spondylitis.

    Serçinoğlu, Onur; Özcan, Gülin; Kabaş, Zeynep Kutlu; Ozbek, Pemra

    2016-07-01

    A single amino acid difference (Asp116His), having a key role in a pathogenesis pathway, distinguishes HLA-B*27:05 and HLA-B*27:09 sub-types as associated and non-associated with ankylosing spondylitis, respectively. In this study, molecular docking simulations were carried out with the aim of comprehending the differences in the binding behavior of both alleles at varying pH conditions. A library of modeled peptides was formed upon single point mutations aiming to address the effect of 20 naturally occurring amino acids at the binding core peptide positions. For both alleles, computational docking was applied using Autodock 4.2. Obtained free energies of binding (FEB) were compared within the peptide library and between the alleles at varying pH conditions. The amino acid preferences of each position were studied enlightening the role of each on binding. The preferred amino acids for each position of pVIPR were found to be harmonious with experimental studies. Our results indicate that, as the pH is lowered, the capacity of HLA-B*27:05 to bind peptides in the library is largely lost. Hydrogen bonding analysis suggests that the interaction between the main anchor positions of pVIPR and their respective binding pocket residues are affected from the pH the most, causing an overall shift in the FEB profiles. PMID:27506766

  17. 强直性脊柱炎患者HLA-B27、B7、B13、B40抗原的表达及免疫学指标分析

    李士军; 王滨; 曹华军

    2002-01-01

    [目的]探讨强直性脊柱炎患者HLA-B27、B7、B13、B40的抗原表达,发现抗原相互杂合与交叉反应,以及强直性脊柱炎患者的免疫学指标的变化。[方法]采用NIH微量淋巴细胞毒法对HLA-B27等抗原进行检测,抗核抗体采用间接免疫荧光法。免疫球蛋白及补体均采用免疫速率散射法测定。[结果]126例初诊患者中HLA-B27阳性率为34.1%,HLA-B27、B13、B40的阳性率分别为6.3%、13.5%、11.1%。HLA-B27阳性组中HLA-B13阳性率为27.9%,HLA-B40阳性率为23.3%,分别高于HLA-B27阴性组(6.0%,4.8%),而HLA-B27的阳性率两组无显著性差异。HLA-B27阳性组的免疫球蛋白、补体、抗核抗体指标均显著高于HLA-B27阴性组(P均<0.05)。[结论]检测强直性脊柱炎患者HLA-B27及相关B抗原有助于疾病诊断和抗原交叉反应的分析。体液免疫异常及自身抗体的出现与HLA-B27密切相关。

  18. Superior oblique tendon (Brown’s syndrome as the presenting finding in childhood onset HLA-B27-related enthesitis and juvenile idiopathic oligoarticular arthritis

    C. Pham

    2014-11-01

    Full Text Available We report two patients who presented with Brown’s syndrome. The first is a 7-year-old boy who at the time of his diagnosis was also found to have enthesitis and HLA-B27 positivity. The second patient was diagnosed with bilateral Brown’s syndrome at 13 months of age. At age 7 she developed a persistent oligoarticular arthritis and unilateral anterior iritis consistent with the oligoarticular Juvenile Idiopatic Arthritis (JIA phenotype. These cases highlight ophthalmologic findings and diagnostic considerations with respect to Brown’s syndrome and associated childhood onset rheumatologic disease.

  19. Cartilage collagen type II seromarker patterns in axial spondyloarthritis and psoriatic arthritis: associations with disease activity, smoking and HLA-B27.

    Munk, Heidi Lausten; Gudmann, Natasja Staehr; Christensen, Anne Friesgaard; Ejstrup, Leif; Sorensen, Grith Lykke; Loft, Anne Gitte; Bay-Jensen, Anne C; Siebuhr, Anne Sofie; Junker, Peter

    2016-04-01

    The aim of the study was to assess the possible association between type II collagen turnover seromarkers and disease profile in patients with axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). Outpatients with axial SpA (n = 110) or PsA (n = 101) underwent clinical examination including disease activity measures and HLA-B27 typing. The procollagen IIA N-terminal peptide (PIIANP) and a matrix metalloproteinase-generated type II collagen fragment (C2M) were quantified in serum by ELISA. C2M was higher in SpA than in controls, 0.41 versus 0.36 ng/ml (p = 0.004), while PIIANP did not differ between patients and healthy subjects, 2252 versus 2142 ng/ml (p = 0.13). However, DMARD-naïve SpA patients had higher PIIANP, 2461 ng/ml (p = 0.01) and C2M, 0.44 ng/ml (p = 0.0007) levels than controls, and PIIANP correlated with CRP (ρ = 0.34). C2M was lower in SpA smokers, 0.36 ng/ml versus non-smokers, 0.43 ng/ml (p = 0.02), while PIIANP was higher in HLA-B27 positive, 2312 ng/ml versus negative patients, 2021 ng/ml (p = 0.03). In PsA, PIIANP and C2M did not differ between patients and controls, but PIIANP was elevated in patients not receiving DMARDs, 2726 ng/ml. In PsA, PIIANP and C2M did not differ according to smoking and HLA-B27. Cartilage degradation assessed by C2M is increased in SpA irrespective of treatment but not in PsA. Cartilage synthesis reflected by PIIANP is increased in untreated SpA and PsA. PIIANP correlates with CRP in SpA while not in PsA. In DMARD-naïve SpA but not in PsA, HLA-B27 positivity and smoking are associated with a chondro-proliferative metabolic pattern. PMID:26620690

  20. Superior oblique tendon (Brown’s) syndrome as the presenting finding in childhood onset HLA-B27-related enthesitis and juvenile idiopathic oligoarticular arthritis

    Pham, C; V. Utz; A. Marcotty; A. Zeft; P. Rychwalski

    2014-01-01

    We report two patients who presented with Brown’s syndrome. The first is a 7-year-old boy who at the time of his diagnosis was also found to have enthesitis and HLA-B27 positivity. The second patient was diagnosed with bilateral Brown’s syndrome at 13 months of age. At age 7 she developed a persistent oligoarticular arthritis and unilateral anterior iritis consistent with the oligoarticular Juvenile Idiopatic Arthritis (JIA) phenotype. These cases highlight ophthalmologic findings and diagnos...

  1. Endoplasmic reticulum aminopeptidase-1 alleles associated with increased risk of Ankylosing Spondylitis reduce HLA-B27 mediated presentation of multiple antigens

    Seregin, Sergey S.; Rastall, David P. W.; Evnouchidou, Irini; Charles F Aylsworth; Quiroga, Dionisia; Kamal, Ram P.; Godbehere-Roosa, Sarah; Blum, Christopher F.; Ian A York; Stratikos, Efstratios; Amalfitano, Andrea

    2013-01-01

    Ankylosing spondylitis (AS) is a chronic systemic arthritic disease that leads to significant disability and loss of quality of life in the ~0.5% of the worldwide human population it affects. There is currently no cure for AS and mechanisms underlying its pathogenesis remain unclear. AS is highly genetic, with over 70% of the genetic risk being associated with the presence of HLA-B27 and endoplasmic reticulum aminopeptidase-1 (ERAP1) alleles. Furthermore, gene-gene interactions between HLA-B2...

  2. An HLA-C amino-acid variant in addition to HLA-B*27 confers risk for ankylosing spondylitis in the Korean population

    Kim, Kwangwoo; Bang, So-Young; Lee, Seunghun; Lee, Hye-Soon; Shim, Seung-Cheol; Kang, Young Mo; Suh, Chang-Hee; Sun, Celi; Nath, Swapan K; Bae, Sang-Cheol; Kim, Tae-Hwan

    2015-01-01

    Introduction The presence of the HLA-B*27 allele is a major risk factor for the development of ankylosing spondylitis (AS), which causes chronic inflammation of the spine and other sites. We investigated residual effects outside HLA-B within the major histocompatibility complex (MHC) region in the Korean population. Methods Using the Korean HLA reference panel, we inferred the classic HLA alleles and amino-acid residues of the six HLA genes (HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1) and MHC sin...

  3. 人白细胞抗原-B27在诊断强直性脊柱炎中的意义%Clinical significance of HLA-B27 test in diagnosis of ankylosing spondylitis

    陈国敏; 王东辰

    2007-01-01

    目的 探讨人白细胞抗原-B27(HLA-B27)检测诊断强直性脊柱炎(AS)的意义.方法 应用ELISA法,对107例AS患者、70例类风湿性关节炎(RA)患者及100例健康体检者进行HLA-B27对比检测.结果 AS组HLA-B27阳性率为92.5%,RA组阳性率为7.1%,体检组阳性率为3.0%,AS组明显高于RA组和体检对照组,差异有统计学意义(χ2=214,P<0.01).男性HLA-B27阳性率(49.7%)明显高于女性(14.8%),差异有统计学意义(χ2=30.9,P<0.01).不同年龄组HLA-B27阳性率有明显差异,30岁以下年龄组明显高于其他年龄组.结论 HLA-B27与AS具有很强的相关性,检测HLA-B27对于AS的早期诊断和鉴别具有重要意义.

  4. Genetic polymorphisms of stromal interaction molecule 1 associated with the erythrocyte sedimentation rate and C-reactive protein in HLA-B27 positive ankylosing spondylitis patients.

    James Cheng-Chung Wei

    Full Text Available Ankylosing spondylitis (AS is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The development of ankylosing spondylitis is still unclear. Genetics factors such as human leukocyte antigen HLA-B27 and ERAP1 have been widely reported to associate to AS susceptibility. In this study, we enrolled 361 AS patients and selected four tagging single nucleotides polymorphisms (tSNPs at STIM1 gene. The correlation between STIM1 genetic polymorphisms and AS activity index (BASDAI, BASFI, BAS-G as well as laboratory parameters of inflammation (erythrocyte sedimentation rate (ESR and C-reactive protein (CRP were tested. Our results indicated that HLA-B27 positive AS patients who are carrying the minor allele homozygous G/G genotype of SNP rs3750996 significantly associated with a higher level of ESR in serum. Furthermore, rs3750996/rs3750994 pairwise allele analysis indicated that G-C haplotypes also significantly correlated with higher level of ESR as well as CRP. These findings provide a better understanding of STIM1 genetic contribution to the pathogenesis of AS.

  5. EVOLUCIÓN DE ARTRITIS PSORIÁSICA A PARTIR DE ESPONDILOARTROPATÍA INDIFERENCIADA NO ASOCIADA AL ANTIGENO HLA-B27: REPORTE DE UN CASO

    Diego Bernardo Alarcón Granados

    2016-07-01

    Full Text Available Paciente masculino, 56 años de edad, cuya enfermedad actual inicia a los 21 años de edad, presentando lumbalgia inflamatoria. Concomitantemente monoartritis en rodilla izquierda, de aparición brusca, limitando su deambulación. Acude a especialista quien evalúa y diagnostica espondiloartropatía indiferenciada. Meses después, reaparecen episodios de lumbalgia inflamatoria por lo que procede a automedicarse. 27 años después presenta prurito en cuero cabelludo y dorso de antebrazo, así como placas eritematosas, descamativas, de tamaño variable, bordes delimitados. Acude a dermatólogo quien diagnostica psoriasis. Meses después, aparecen lesiones de psoriasis generalizadas, oligoartritis y lumbalgia mecánica. Es reevaluado diagnosticándose artritis psoriásica. Actualmente, presenta perdida de la lordosis lumbar, sindesmofitos y sacroileítis bilateral como hallazgos radiológicos. La población afectada por artritis psoriásica oscila entre 0,02 al 0,42%; en un 17% de los casos la artritis precede a la psoriasis. Los casos con espondilitis se asocian a sacroileítis y HLA-B27 positivo; sólo 10% de las espondilitis presenta HLA-B27 negativo. Palabras Clave: Artritis Psoriásica, espondiloartropatía, psoriasis.

  6. In vivo functions of CPSF6 for HIV-1 as revealed by HIV-1 capsid evolution in HLA-B27-positive subjects.

    Matthew S Henning

    2014-01-01

    Full Text Available The host protein CPSF6 possesses a domain that can interact with the HIV-1 capsid (CA protein. CPSF6 has been implicated in regulating HIV-1 nuclear entry. However, its functional significance for HIV-1 replication has yet to be firmly established. Here we provide evidence for two divergent functions of CPSF6 for HIV-1 replication in vivo. We demonstrate that endogenous CPSF6 exerts an inhibitory effect on naturally occurring HIV-1 variants in individuals carrying the HLA-B27 allele. Conversely, we find a strong selective pressure in these individuals to preserve CPSF6 binding, while escaping from the restrictive activity by CPSF6. This active maintenance of CPSF6 binding during HIV-1 CA evolution in vivo contrasts with the in vitro viral evolution, which can reduce CPSF6 binding to evade from CPSF6-mediated restriction. Thus, these observations argue for a beneficial role of CPSF6 for HIV-1 in vivo. CPSF6-mediated restriction renders HIV-1 less dependent or independent from TNPO3, RanBP2 and Nup153, host factors implicated in HIV-1 nuclear entry. However, viral evolution that maintains CPSF6 binding in HLA-B27+ subjects invariably restores the ability to utilize these host factors, which may be the major selective pressure for CPSF6 binding in vivo. Our study uncovers two opposing CA-dependent functions of CPSF6 in HIV-1 replication in vivo; however, the benefit for binding CPSF6 appears to outweigh the cost, providing support for a vital function of CPSF6 during HIV-1 replication in vivo.

  7. 强直性脊柱炎患者HLA-B27抗原表达与骨损害关系的临床研究%Clinical study of relationship between HLA-B27 antigen expression and bone damage in patients of ankylosing spondylitis

    王丽; 陈程; 杨忠礼

    2005-01-01

    目的探讨HLA-B27表达与强直性脊柱炎患者骨代谢功能损伤的关系.方法检测HLA-B27不同型别的强直性脊柱炎患者和对照群体骨代谢功能指标.结果研究显示各组间各项指标存在着不同程度的统计学差异,具体表现为:CK检测水平B27+AS>B27-AS和B27-对照(P<0.05),而B27+AS和B27-对照之间无显著差异(P>0.05);AKP检测水平B27+AS>B27-AS>B27+对照和B27-对照(P<0.05),而B27+对照和B27对照之间无显著差异(P>0.05);CT检测水平B27+AS>B27-AS>B27+对照>B27-对照(P<0.05):BGP检测水平B27+AS>B27-AS>B27+对照>B27-对照(P<0.01).结论强直性脊柱炎患者HLA-B27的表达与骨质损害具有一定的关联性,为临床深入研究提供了有益的线索.

  8. Genetic markers as a predictive tool based on statistics in medical practice: ethical considerations through the analysis of the use of HLA-B27 in rheumatology in France

    Hélène eColineaux

    2015-10-01

    Full Text Available INTRODUCTION. The use of genetic predictive markers in medical practice does not necessarily bear the same kind of medical and ethical consequences than that of genes directly involved in monogenic diseases. However, the French bioethics law framed in the same way the production and use of any genetic information. It seems therefore necessary to explore the practical and ethical context of the actual use of predictive markers in order to highlight their specific stakes. In this study, we document the uses of HLA-B*27, which are an interesting example of the multiple features of genetic predictive marker in general medical practice.MATERIAL & METHODS. The aims of this monocentric and qualitative study were to identify concrete and ethical issues of using the HLA-B*27 marker and the interests and limits of the legal framework as perceived by prescribers. In this regard, a thematic and descriptive analysis of five rheumatologists’ semi-structured and face-to-face interviews was performed.RESULTS. According to most of the interviewees, HLA-B*27 is an overframed test because they considered that this test is not really genetic or at least does not have the same nature as classical genetic tests; HLA-B*27 is not concerned by the ethical challenges of genetic test; the major ethics stake of this marker is not linked to its genetic nature but rather to the complexity of the probabilistic information. This study allows also showing that HLA-B*27, validated for a certain usage, may be used in different ways in practice.DISCUSSION. This marker and its clinical uses underline the challenges of translating both statistical concepts and unifying legal framework in clinical practice. This study allows identifying some new aspects and stakes of genetics in medicine and shows the need of additional studies about the use of predictive genetic markers, in order to provide a better basis for decisions and legal framework regarding these practices.

  9. HLA-B27基因亚型、KIR基因和HLA-Cw基因与强直性脊柱炎病情活动的关系%The Relationship of the Subtypes of HLA-B27,HLA-Cw and KIRs with the Activity of Ankylosing Spondylitis

    张谷香; 赵福涛

    2016-01-01

    Objective To study the association of the polymorphism of human leukocyte antigen-B27 (HLA-B27),Killer immunoglobulin receptor(KIR),and human leukocyte antigen-Cw(HLA-Cw) genes with the activity of ankylosing spondylitis(AS).Methods Total of 25 patients with active AS admitted to Shanghai Third People′s Hospital Affiliated to Shanghai Jiaotong University from Jun .2011 to Mar.2013 were selected as trial group,41 patients with stable AS were inlcuded as control group.HLA-B27 subtype,KIR gene and HLA-Cw gene were detected by polymerase chain reaction with with sequence-specific primers (PCR-SSP).Results The gene frequency of HLA-Cw02,HLA-Cwlys and KIR3DS1 in the trial group were significantly higher than those in the control group[44.0%(11/25)vs 15.4%(6/41),48.0%(12/25) vs 22.0%(9/41),68.0%(17/25) vs 41.5%(17/41)],the differences were statistically significant(P <0.05).Conclusion The dramatic increase of frequencies of KIR3DS1,HLA-Cw02 and HLA-Cwlys in the active AS patients indicates KIRs gene and HLA-Cw gene is associated with the activity of AS .%目的 分析人类白细胞抗原( HLA)-B27 基因多态性、杀伤细胞免疫球蛋白样受体( KIR)基因和HLA-Cw基因与强直性脊柱炎( AS)病情活动的关系. 方法 选择2011 年6 月至2013 年3月上海交通大学医学院附属第三人民医院收治的活动期 AS患者25 例作为试验组,稳定期 AS患者41例作为对照组,采用特异性引物聚合酶链反应( PCR-SSP )技术进行 HLA-B27 亚型、KIR 基因、HLA-Cw基因检测. 结果 试验组 HLA-Cw02 和 HLA-Cwlys、 KIR3DS1 的基因频率显著高于对照组[44.0%(11/25)比15.4%(6/41),48.0%(12/25)比22.0%(9/41),68.0%(17/25)比41.5%(17/41)],差异有统计学意义(P<0.05). 结论 HLA-Cw02 和 HLA-Cwlys、KIR3DS1 基因频率在活动期AS患者中明显增高,表明KIRs基因和HLA-Cw基因与AS的病情活动有关.

  10. The study between the gene and the subtypes of HLA-1327 and ankylosing spondylitis in Hainan%海南地区HLA-B27及其亚型与强直性脊椎炎相关性研究

    徐卫华; 符生苗; 赵英

    2008-01-01

    目的 通过检测海南地区20个AS患者家族的HLA-B27基因,以获得HLA-B27抗原以及基因亚型的分布情况.方法 B27抗原检测和基因亚型检测均采用序列特异性引物聚合酶链式反应(PCR-SSR)技术.结果 B27阳性者患AS的概率为57.7%,其中男女比例约为3.6:1,AS患者中HLA-B27阳性者占93.2%,阳性与阴性的患病比例高达14:1.AS患者一级亲属HLA-B27阳性率52.7%,患病率21.6%,HLA-B27阳性者其后代仍为阳性的概率55.4%;基因分型均为HLA-B2704亚型.结论 海南地区HLA-B27阳性和As发病率均与性别有关,并具有家族遗传性,HLA-B27基因亚型为132704.

  11. Peptide-binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes and include HLA-B27-like alleles

    Mothé, Bianca R.; Southwood, Scott; Sidney, John;

    2013-01-01

    deciphering outcomes of infection and vaccine efficacy. In this study, we have provided detailed characterization of six prevalent Chinese rhesus macaque MHC class I alleles, yielding a combined phenotypic frequency of 29 %. The peptide-binding specificity of two of these alleles, Mamu-A2*01:02 and Mamu-B*010......:01, as well as the previously characterized allele Mamu-B*003:01 (and Indian rhesus Mamu-B*003:01), was found to be analogous to that of alleles in the HLA-B27 supertype family. Specific alleles in the HLA-B27 supertype family, including HLA-B*27:05, have been associated with long-term nonprogression to...... AIDS in humans. All six alleles characterized in the present study were found to have specificities analogous to HLA supertype alleles. These data contribute to the concept that Chinese rhesus macaque MHC immunogenetics is more similar to HLA than their Indian rhesus macaque counterparts and thereby...

  12. Generation of Transgenic Rats Using Lentiviral Vectors.

    Reichardt, Holger M; Fischer, Henrike J

    2016-01-01

    Transgenesis is a valuable tool with which to study different aspects of gene function in the context of the intact organism. During the last two decades a tremendous number of transgenic animals have been generated, and the continuous improvement of technology and the development of new systems have fostered their widespread application in biomedical research. Generally, transgenic animals are generated by introducing foreign DNA into fertilized oocytes, which can be achieved either by injecting recombinant DNA into the pronucleus or by transferring lentiviral particles into the perivitelline space. While mice remain the favored species in many laboratories, there are a number of applications where the use of rats is advantageous. One such research area is multiple sclerosis. Here, several experimental models are available that are closely mimicking the human disease, and it is possible to induce neuroinflammation by transferring pathogenic T cells which can then be studied by flow cytometry and 2-photon live imaging. Unlike for mice, the development of transgenic rats has encountered some hurdles in the past, e.g., due to a complicated reproductive biology and the frailty of the fertilized oocytes in vitro. In this chapter we provide a protocol describing how we manipulate single cell embryos in our lab in order to efficiently generate transgenic rats in a variety of different strains using lentiviral gene transfer. PMID:25063498

  13. Detection of HLA-B27 and genetic subtypes in young soldiers with low back pain%青壮年军人腰腿痛患者 HLA-B27及其基因亚型检测分析

    高文博; 徐海栋; 刘刚; 李卫巍; 夏欣一; 虞伟; 李晓军

    2015-01-01

    目的:通过检测2126例青壮年军人腰腿痛患者人类白细胞抗原B27( HLA-B27)阳性率和表达强度,了解本地区军人强直性脊柱炎( ankylosing spondylitis,AS)与HLA-B27抗原相关性,并初步探讨其对AS的临床诊断意义;通过检测确诊AS军人患者HLA-B27基因亚型,了解本地区军人HLA-B27基因亚型分布情况。方法用流式细胞仪分析2013年8月1日-2014年1月10日2126例因腰腿痛入南京军区南京总医院就诊的军人患者HLA-B27抗原表达情况;用荧光定量PCR法对其中确诊AS患者HLA-B27基因亚型进行检测分析。结果2126例患者中HLA-B27阳性者158例,阳性率为7.4%,男女患者HLA-B27抗原阳性率分别为7.1%和10.0%(P<0.01);33例HLA-B27阳性确诊患者中,B*2704和为B*2705为主要型别,分别占51.5%和42.4%。结论 HLA-B27对于AS仅有辅助诊断作用,不宜作为AS的常规筛选指标。%Objective To investigate the relationship and diagnostic significance between ankylosing spondylitis and HLA-B27 antigen in soldiers in one military district by detecting the positive rate and expression intensity of HLA-B27 antigen in 2126 young soldiers with low back pain, and evaluate its clinical significance.To investigate the distribution of genetic subtypes of AS by detecting genetic subtypes of HLA-B27 in confirmed soldiers.Methods The expression of HLA-B27 antigen of peripheral blood T lymphocytes in 2126 hospital admission patients was analyzed by flow cytometry.Genetic subtypes of HLA-B27 was determined by fluorescence quantitative polymerase chain reaction assay.Results 158 patients were positive in 2126 patients.The positive rate of antigen HLA-B27 was 7.4%, and the male and female patientsˊpositive rates of HLA-B27 antigen were 7.1% and 10.0%, respectively ( P<0.01).Among the 33 confirmed AS patients with HLA-B27 antigen positivity, B*2704 and B*2705 were the main type with

  14. HLA B27 related 'unclassifiable' seronegative spondyloarthropathies.

    Prakash, S.; Mehra, N. K.; Bhargava, S; Malaviya, A N

    1983-01-01

    Twenty-five patients (22 males and 3 females) are described who had 'unclassifiable' seronegative peripheral arthritis affecting mainly the large joints of the lower limbs with other typical features of spondyloarthropathies such as heel pain, low back pain, and mucosal ulcers. But their disorders could not be diagnosed as any specific spondyloarthropathy such as ankylosing spondylitis, Reiter's disease, etc. The mean age of onset of disease was 21.4 years and 60% of them had mono- or oligoar...

  15. Inducible gene manipulations in brain serotonergic neurons of transgenic rats.

    Tillmann Weber

    Full Text Available The serotonergic (5-HT system has been implicated in various physiological processes and neuropsychiatric disorders, but in many aspects its role in normal and pathologic brain function is still unclear. One reason for this might be the lack of appropriate animal models which can address the complexity of physiological and pathophysiological 5-HT functioning. In this respect, rats offer many advantages over mice as they have been the animal of choice for sophisticated neurophysiological and behavioral studies. However, only recently technologies for the targeted and tissue specific modification of rat genes - a prerequisite for a detailed study of the 5-HT system - have been successfully developed. Here, we describe a rat transgenic system for inducible gene manipulations in 5-HT neurons. We generated a Cre driver line consisting of a tamoxifen-inducible CreERT2 recombinase under the control of mouse Tph2 regulatory sequences. Tissue-specific serotonergic Cre recombinase expression was detected in four transgenic TPH2-CreERT2 rat founder lines. For functional analysis of Cre-mediated recombination, we used a rat Cre reporter line (CAG-loxP.EGFP, in which EGFP is expressed after Cre-mediated removal of a loxP-flanked lacZ STOP cassette. We show an in-depth characterisation of this rat Cre reporter line and demonstrate its applicability for monitoring Cre-mediated recombination in all major neuronal subpopulations of the rat brain. Upon tamoxifen induction, double transgenic TPH2-CreERT2/CAG-loxP.EGFP rats show selective and efficient EGFP expression in 5-HT neurons. Without tamoxifen administration, EGFP is only expressed in few 5-HT neurons which confirms minimal background recombination. This 5-HT neuron specific CreERT2 line allows Cre-mediated, inducible gene deletion or gene overexpression in transgenic rats which provides new opportunities to decipher the complex functions of the mammalian serotonergic system.

  16. Promising future for the transgenic rat in transplantation research.

    Doorschodt, B M; Teubner, A; Kobayashi, E; Tolba, R H

    2014-10-01

    The rat is the most widely used animal species in surgical research and offers distinct advantages over the mouse in transplantation models due to its size and close genetic similarity to humans. Sequencing of the rat genome and successful application of transgenic technologies which had only been available for mice have since led to a resurgence of the use of rat models. Transplantation provides the possibility to deliver transgenes through a variety of routes which can potentially offer treatment modalities for post-transplant dysfunction and rejection. Moreover, the use of genetically encoded fluorescent light probes has enabled in vivo visualization of organs and tissue in living animals. In recent years, generation of gene knockout rats via the zinc-finger nuclease (ZFN) and transcription activator-like effector nuclease (TALEN) technologies has offered alternatives to the sophisticated embryonic stem cell based gene-targeting. In this review, we aim to provide an overview of transplantation studies involving transgenic techniques using rat models and recent advances in methods to modify the rat genome. Through novel gene modification techniques, precise, complete and conditional knockout and knockin rat models have become available which can provide promising new treatment options and opportunities for studying human transplant-related pathophysiology. PMID:24975516

  17. Immunodeficient Parameters in the HIV-1 Transgenic Rat Model

    Sulie L. Chang

    2007-01-01

    Full Text Available Recently an HIV-1 transgenic (HIV-1Tg rat model was created that carries a gag-pol-deleted HIV-1 genome under the control of the HIV-1 viral promoter. However, other viral proteins are expressed in most organs and tissues, and are found in the circulating blood. Since HIV-1 targets the immune system in humans, we examined two immunological parameters, leukocyte-endothelial adhesion (LEA and inflammatory cytokine production, in 5 mo old HIV-1Tg rats to identify immune functions that may be impaired even before the onset of symptoms of HIV-1 infection. We administered a single injection (i.p. of the bacterial endotoxin, lipopolysaccharide (LPS, 250 ug/kg, to 5 mo old HIV-1Tg rats, age-matched transgenic control (Tg rats, and F344/NHsd (F344 control background strain rats. LPS induced an LEA response in both the Tg control and F344 control animals. However, in the HIV-1Tg rats, there was no LEA response to LPS. Following LPS administration, there was significantly greater serum levels of TNF-α and IL-1β, two pro-inflammatory cytokines, in the HIV-1Tg rats compared to the control animals. In contrast, the serum level of IL-10, an anti-inflammatory cytokine, was comparable in the HIV-1Tg, Tg control, and F344 control rats. Our data show that, in the HIV-1Tg rat, there is a negative correlation between the LEA response and the induction of pro-inflammatory cytokines in response to bacterial endotoxin. These findings suggest that the persistent presence of viral proteins may be, at least, partially responsible for the immunodeficiency that occurs with HIV-1 infection, and that the HIV-1Tg rat could be a valid rodent model in which to study various aspects of HIV-1 infection.

  18. A transgenic rat with ubiquitous expression of firefly luciferase gene

    Hakamata, Yoji; Murakami, Takashi; Kobayashi, Eiji

    2006-02-01

    In vivo imaging strategies provide cellular and molecular events in real time that helps us to understand biological processes in living animals. The development of molecular tags such as green fluorescent proteins and luciferase from the firefly Photinus pyralis has lead to a revolution in the visualization of complex biochemical processes. We developed a novel inbred transgenic rat strain containing firefly luciferase based on the transgenic (Tg) technique in rats. This Tg rat expressed the luciferase gene ubiquitously under control of the ROSA26 promoter. Cellular immune responsiveness against the luciferase protein was evaluated using conventional skin grafting and resulted in the long-term acceptance of Tg rat skin on wild-type rats. Strikingly, organ transplant with heart and small bowel demonstrated organ viability and graft survival, suggesting that cells from luciferase-Tg are transplantable to track their fate. Taking advantage of the less immunogenic luciferase, we also tested the role of hepatocyte-infusion in a liver injury model, and bone marrow-derived cells in a skin defect model. Employed in conjunction with modern advances in optical imaging, this luciferase-Tg rat system provides an innovative animal tool and a new means of facilitating biomedical research such as in the case of regeneration medicine.

  19. Immunodeficient Parameters in the HIV-1 Transgenic Rat Model

    Chang, Sulie L.; Frank Ocasio; Joseq A. Beltran

    2007-01-01

    Recently an HIV-1 transgenic (HIV-1Tg) rat model was created that carries a gag-pol-deleted HIV-1 genome under the control of the HIV-1 viral promoter. However, other viral proteins are expressed in most organs and tissues, and are found in the circulating blood. Since HIV-1 targets the immune system in humans, we examined two immunological parameters, leukocyte-endothelial adhesion (LEA) and inflammatory cytokine production, in 5 mo old HIV-1Tg rats to identify immune functions that may be i...

  20. Developing tTA Transgenic Rats for Inducible and Reversible Gene Expression

    Hongxia Zhou, Cao Huang, Min Yang, Carlisle P Landel, Pedro Yuxing Xia, Yong-Jian Liu, Xu Gang Xia

    2009-01-01

    To develop transgenic lines for conditional expression of desired genes in rats, we generated several lines of the transgenic rats carrying the tetracycline-controlled transactivator (tTA) gene. Using a vigorous, ubiquitous promoter to drive the tTA transgene, we obtained widespread expression of tTA in various tissues. Expression of tTA was sufficient to strongly activate its reporter gene, but was below the toxicity threshold. We examined the dynamics of Doxycycline (Dox)-regulated gene exp...

  1. PP005. Vitamin D depletion aggravates hypertension in transgenic rats

    Bjørkholt Andersen, Louise; Herse, Florian; Christesen, Henrik Thybo;

    2013-01-01

    overexpressing the human renin and angiotensinogen genes, group 1 (n=18) received vitamin D depleted chow; group 2 (n=15) standard chow and intraperitoneal paricalcitol at 800ng/kg thrice weekly; and group 3 (n=15) standard chow and vehicle injections. Blood pressure (tail cuff) and 24-h albuminuria were......INTRODUCTION: Vitamin D may ameliorate hypertension and kidney disease through genomic and extra-genomic pathways. OBJECTIVE: To investigate the impact of vitamin D in a transgenic rat model of angiotensin II-mediated hypertensive organ failure. METHODS: In 4-week-old age-matched rats...... determined once weekly. After three weeks, animals were sacrificed. Heart tissue was examined for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) by RT-PCR. RESULTS: The vitamin D depleted group had higher blood pressure at week 1 (mean difference 23.4mmHg, 95% CI 9.1-37.7) and tended to...

  2. Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats

    Haller Hermann; Ganten Detlev; Barta Peter; Fiebeler Anette; Park Joon-Keun; Muller Dominik N; Dechend Ralf; Theuer Juergen; Dietz Rainer; Luft Friedrich C

    2002-01-01

    BACKGROUND: We are investigating a double transgenic rat (dTGR) model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1) are expressed early on the endothelium, while the corresponding ligands are ...

  3. Inducible Transgenic Rat Model for Diabetes Mellitus Based on shRNA-Mediated Gene Knockdown

    Katarina Kotnik; Elena Popova; Mihail Todiras; Mori, Marcelo A.; Natalia Alenina; Jost Seibler; Michael Bader

    2009-01-01

    The rat is an important animal model in biomedical research, but gene targeting technology is not established for this species. Therefore, we aimed to produce transgenic knockdown rats using shRNA technology and pronuclear microinjection. To this purpose, we employed a tetracycline-inducible shRNA expression system targeting the insulin receptor (IR). Doxycycline (DOX) treatment of the resulting transgenic rats led to a dose-dependent and reversible increase in blood glucose caused by ubiquit...

  4. A promoter that drives gene expression preferentially in male transgenic rats

    Li, Qiling; Ma, Yamin; Li, Wenzhi; Xu, Wei; Ma, Li; Fu, Guoxing; Tian, Xiaohua; Wang, Yueling; Li, Xu; Bythwood, Tameka; Richards, Jendai; Song, Qing

    2013-01-01

    Gender-preferential gene expression is a widespread phenomenon in humans. It is important to study how gender differences influence the pathogenesis of various diseases and response to specific drugs. The aim of this study is to determine if the mouse albumin enhancer/promoter may serve as the promoter to introduce gender-preferential gene expression in transgenic animals. We created four independent transgenic rat lines in which the human C-reactive protein (CRP) transgene was under the cont...

  5. Prostate carcinoma in transgenic Lewis rats - a tumor model for evaluation of immunological treatments

    Johnson, Laura E.; Becker, Jordan T; Dubovsky, Jason A.; Olson, Brian M.; McNeel, Douglas G.

    2013-01-01

    Transgenic rodent models of prostate cancer have served as valuable preclinical models to evaluate novel treatments and understand malignant disease progression. In particular, a transgenic rat autochthonous model of prostate cancer using the SV40 large T antigen expressed under a prostate-specific probasin promoter was previously developed as a model of androgen-dependent prostate cancer (TRAP). In the current report, we backcrossed this strain to the Lewis strain, an inbred rat strain bette...

  6. Regulatory regions of rat insulin I gene necessary for expression in transgenic mice.

    Dandoy-Dron, F; Monthioux, E; Jami, J; Bucchini, D

    1991-01-01

    Ten transgenic mouse lines harboring the -346/-103 fragment of the rat insulin I enhancer linked to a heterologous promoter and a reporter gene (Eins-Ptk-CAT construct) were produced. Expression of the hybrid transgene was essentially observed in pancreas and to a lesser extent in brain. These results indicate that the rat insulin I promoter is dispensable for pancreatic expression. This insulin gene sequence is the shortest fragment described as conferring tissue-specific expression in trans...

  7. Efficient Production of Fluorescent Transgenic Rats using the piggyBac Transposon.

    Li, Tianda; Shuai, Ling; Mao, Junjie; Wang, Xuepeng; Wang, Mei; Zhang, Xinxin; Wang, Leyun; Li, Yanni; Li, Wei; Zhou, Qi

    2016-01-01

    Rats with fluorescent markers are of great value for studies that trace lineage-specific development, particularly those assessing the differentiation potential of embryonic stem cells (ESCs). The piggyBac (PB) transposon is widely used for the efficient introduction of genetic modifications into genomes, and has already been successfully used to produce transgenic mice and rats. Here, we generated transgenic rats carrying either the desRed fluorescent protein (RFP) gene or the enhanced green fluorescent protein (eGFP) gene by injecting pronuclei with PB plasmids. We showed that the transgenic rats expressed the RFP or eGFP gene in many organs and had the capability to transmit the marker gene to the next generation through germline integration. In addition, rat embryonic stem cells (ESCs) carrying an RFP reporter gene can be derived from the blastocysts of the transgenic rats. Moreover, the RFP gene can be detected in chimeras derived from RFP ESCs via blastocyst injection. This work suggests that PB-mediated transgenesis is a powerful tool to generate transgenic rats expressing fluorescent proteins with high efficiency, and this technique can be used to derive rat ESCs expressing a reporter protein. PMID:27624004

  8. Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.

    Katarina Kotnik

    Full Text Available The rat is an important animal model in biomedical research, but gene targeting technology is not established for this species. Therefore, we aimed to produce transgenic knockdown rats using shRNA technology and pronuclear microinjection. To this purpose, we employed a tetracycline-inducible shRNA expression system targeting the insulin receptor (IR. Doxycycline (DOX treatment of the resulting transgenic rats led to a dose-dependent and reversible increase in blood glucose caused by ubiquitous inhibition of IR expression and signalling. We could neither detect an interferon response nor disturbances in microRNA processing after DOX treatment excluding toxic effects of shRNA expression. Low dose DOX treatment induced a chronic state of diabetes mellitus. In conclusion, we have developed a technology which allows the specific, inducible, and reversible suppression of any gene of interest in the rat. Our first transgenic rat line generated with this method represents an inducible model for diabetes mellitus.

  9. A Novel Model of Intravital Platelet Imaging Using CD41-ZsGreen1 Transgenic Rats

    Mizuno, Makoto; Tomizawa, Atsuyuki; Ohno, Kousaku; Jakubowski, Joseph A.; Sugidachi, Atsuhiro

    2016-01-01

    Platelets play pivotal roles in both hemostasis and thrombosis. Although models of intravital platelet imaging are available for thrombosis studies in mice, few are available for rat studies. The present effort aimed to generate fluorescent platelets in rats and assess their dynamics in a rat model of arterial injury. We generated CD41-ZsGreen1 transgenic rats, in which green fluorescence protein ZsGreen1 was expressed specifically in megakaryocytes and thus platelets. The transgenic rats exhibited normal hematological and biochemical values with the exception of body weight and erythroid parameters, which were slightly lower than those of wild-type rats. Platelet aggregation, induced by 20 μM ADP and 10 μg/ml collagen, and blood clotting times were not significantly different between transgenic and wild-type rats. Saphenous arteries of transgenic rats were injured with 10% FeCl3, and the formation of fluorescent thrombi was evaluated using confocal microscopy. FeCl3 caused time-dependent increases in the mean fluorescence intensity of injured arteries of vehicle-treated rats. Prasugrel (3 mg/kg, p.o.), administered 2 h before FeCl3, significantly inhibited fluorescence compared with vehicle-treated rats (4.5 ± 0.4 vs. 14.9 ± 2.4 arbitrary fluorescence units at 30 min, respectively, n = 8, P = 0.0037). These data indicate that CD41-ZsGreen1 transgenic rats represent a useful model for intravital imaging of platelet-mediated thrombus formation and the evaluation of antithrombotic agents. PMID:27128503

  10. A Novel Model of Intravital Platelet Imaging Using CD41-ZsGreen1 Transgenic Rats.

    Makoto Mizuno

    Full Text Available Platelets play pivotal roles in both hemostasis and thrombosis. Although models of intravital platelet imaging are available for thrombosis studies in mice, few are available for rat studies. The present effort aimed to generate fluorescent platelets in rats and assess their dynamics in a rat model of arterial injury. We generated CD41-ZsGreen1 transgenic rats, in which green fluorescence protein ZsGreen1 was expressed specifically in megakaryocytes and thus platelets. The transgenic rats exhibited normal hematological and biochemical values with the exception of body weight and erythroid parameters, which were slightly lower than those of wild-type rats. Platelet aggregation, induced by 20 μM ADP and 10 μg/ml collagen, and blood clotting times were not significantly different between transgenic and wild-type rats. Saphenous arteries of transgenic rats were injured with 10% FeCl3, and the formation of fluorescent thrombi was evaluated using confocal microscopy. FeCl3 caused time-dependent increases in the mean fluorescence intensity of injured arteries of vehicle-treated rats. Prasugrel (3 mg/kg, p.o., administered 2 h before FeCl3, significantly inhibited fluorescence compared with vehicle-treated rats (4.5 ± 0.4 vs. 14.9 ± 2.4 arbitrary fluorescence units at 30 min, respectively, n = 8, P = 0.0037. These data indicate that CD41-ZsGreen1 transgenic rats represent a useful model for intravital imaging of platelet-mediated thrombus formation and the evaluation of antithrombotic agents.

  11. Cognitive impairment in the Tg6590 transgenic rat model of Alzheimer's disease

    Kloskowska, Ewa; Pham, Therese M; Nilsson, Tatjana;

    2010-01-01

    Recently, interest in the rat as an animal model of Alzheimer's disease (AD) has been growing. We have previously described the Tg6590 transgenic rat line expressing the amyloid precursor protein containing the Swedish AD mutation (K670M/N671L) that shows early stages of Abeta deposition...

  12. Transgenic rats with green, red, and blue fluorescence: powerful tools for bioimaging, cell trafficking, and differentiation

    Murakami, Takashi; Kobayashi, Eiji

    2005-04-01

    The rat represents a perfect animal for broadening medical experiments, because its physiology has been well understood in the history of experimental animals. In addition, its larger body size takes enough advantage for surgical manipulation, compared to the mouse. Many rat models mimicking human diseases, therefore, have been used in a variety of biomedical studies including physiology, pharmacology, transplantation, and immunology. In an effort to create the specifically designed rats for biomedical research and regenerative medicine, we have developed the engineered rat system on the basis of transgenic technology and succeeded in establishing various transgenic rat strains. The transgenic rats with green fluorescent protein (GFP) were generated in the two different strains (Wistar and Lewis), in which GFP is driven under the chicken beta-actin promoter and cytomegalovirus enhancer (CAG promoter). Their GFP expression levels were different in each organ, but the Lewis line expressed GFP strongly and ubiquitously in most of the organs compared with that of Wistar. For red fluorescence, DsRed2 was transduced to the Wistar rats: one line specifically expresses DsRed2 in the liver under the mouse albumin promoter, another is designed for the Cre/LoxP system as the double reporter rat (the initial DsRed2 expression turns on GFP in the presence of Cre recombinase). LacZ-transgenic rats represent blue color, and LacZ is driven the CAG (DA) or ROSA26 promoter (Lewis). Our unique transgenic rats" system highlights the powerful performance for the elucidation of many cellular processes in regenerative medicine, leading to innovative medical treatments.

  13. Establishment of an Invasive Prostate Cancer Model in Transgenic Rats by Intermittent Testosterone Administration

    SATO, SHINYA; Suzuki, Shugo; Naiki-Ito, Aya; Komiya, Masami; Ne, Long; Kato, Hiroyuki; Sagawa, Hiroyuki; Yamashita, Yoriko; Shirai, Tomoyuki; Takahashi, Satoru

    2014-01-01

    We have established a transgenic rat for adenocarcinoma of the prostate (TRAP) model that features uniform adenocarcinoma development in prostatic lobes at high incidence within a short experimental period. However, no invasive carcinomas with reactive stroma characteristics similar to those in man were observed. We therefore have focused on a new model for invasive carcinoma of the prostate using TRAP rats. In experiment 1, male TRAP rats in groups 1 and 2 were treated with orchiectomy at da...

  14. Light-sheet microscopy imaging of a whole cleared rat brain with Thy1-GFP transgene

    Marzena Stefaniuk; Gualda, Emilio J.; Monika Pawlowska; Diana Legutko; Paweł Matryba; Paulina Koza; Witold Konopka; Dorota Owczarek; Marcin Wawrzyniak; Pablo Loza-Alvarez; Leszek Kaczmarek

    2016-01-01

    Whole-brain imaging with light-sheet fluorescence microscopy and optically cleared tissue is a new, rapidly developing research field. Whereas successful attempts to clear and image mouse brain have been reported, a similar result for rats has proven difficult to achieve. Herein, we report on creating novel transgenic rat harboring fluorescent reporter GFP under control of neuronal gene promoter. We then present data on clearing the rat brain, showing that FluoClearBABB was found superior ove...

  15. An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction

    Reid, W.; Sadowska, M.; Denaro, F.; Rao, S; Foulke, J.; N. Hayes; Jones, O; Doodnauth, D.; Davis, H.; Sill, A.; O'Driscoll, P.; Huso, D.; Fouts, T.; Lewis, G.(Department of Physics, New York University, New York, NY, United States of America); Hill, M.

    2001-01-01

    We report, to our knowledge, the first HIV type 1 (HIV-1) transgenic (Tg) rat. Expression of the transgene, consisting of an HIV-1 provirus with a functional deletion of gag and pol, is regulated by the viral long terminal repeat. Spliced and unspliced viral transcripts were expressed in lymph nodes, thymus, liver, kidney, and spleen, suggesting that Tat and Rev are functional. Viral proteins were identified in spleen tissue sections by immunohistochemistry and gp120 was present in splenic ma...

  16. Polyethylenimine-mediated expression of transgenes in the acinar cells of rats salivary glands in vivo

    Sramkova, Monika; Parente, Laura; Wigand, Timothy; Aye, Myo-Pale'; Shitara, Akiko; Weigert, Roberto

    2015-01-01

    Non viral-mediated transfection of plasmid DNA provides a fast and reliable way to express various transgenes in selected cell populations in live animals. Here, we show an improvement of a previously published method that is based on injecting plasmid DNA into the ductal system of the salivary glands in live rats. Specifically, using complexes between plasmid DNA and polyethyleneimine (PEI) we show that the expression of the transgenes is directed selectively to the salivary acinar cells. PE...

  17. Generation and characterization of a Tet-On (rtTA-M2) transgenic rat

    Sukhwani Meena; Yue Junming; Lin Chih-Cheng; Sheng Yi; Shuttleworth Jennifer J; Chu Tianjiao; Orwig Kyle E

    2010-01-01

    Abstract Background The tetracycline-inducible gene regulation system is a powerful tool that allows temporal and dose-dependent regulation of target transgene expression in vitro and in vivo. Several tetracycline-inducible transgenic mouse models have been described with ubiquitous or tissue-specific expression of tetracycline-transactivator (tTA), reverse tetracycline-transactivator (rtTA) or Tet repressor (TetR). Here we describe a Tet-On transgenic rat that ubiquitously expresses rtTA-M2 ...

  18. Generation and characterization of a Tet-On (rtTA-M2 transgenic rat

    Sukhwani Meena

    2010-02-01

    Full Text Available Abstract Background The tetracycline-inducible gene regulation system is a powerful tool that allows temporal and dose-dependent regulation of target transgene expression in vitro and in vivo. Several tetracycline-inducible transgenic mouse models have been described with ubiquitous or tissue-specific expression of tetracycline-transactivator (tTA, reverse tetracycline-transactivator (rtTA or Tet repressor (TetR. Here we describe a Tet-On transgenic rat that ubiquitously expresses rtTA-M2 driven by the murine ROSA 26 promoter. Results The homozygous rat line (ROSA-rtTA-M2 generated by lentiviral vector injection, has a single integration site and was derived from the offspring of a genetic mosaic founder with multiple transgene integrations. The rtTA-M2 transgene integrated into an intron of a putative gene on chromosome 2 and does not appear to affect the tissue-specificity or expression of that gene. Fibroblasts from the ROSA-rtTA-M2 rats were transduced with a TetO7/CMV-EGFP lentivirus and exhibited doxycycline dose-dependent expression of the EGFP reporter transgene, in vitro. In addition, doxycycline-inducible EGFP expression was observed, in vivo, when the TetO7/CMV-EGFP lentivirus was injected into testis, kidney and muscle tissues of ROSA-rtTA-M2 rats. Conclusions This conditional expression rat model may have application for transgenic overexpression or knockdown studies of gene function in development, disease and gene therapy.

  19. Developing tTA Transgenic Rats for Inducible and Reversible Gene Expression

    Hongxia Zhou, Cao Huang, Min Yang, Carlisle P Landel, Pedro Yuxing Xia, Yong-Jian Liu, Xu Gang Xia

    2009-01-01

    Full Text Available To develop transgenic lines for conditional expression of desired genes in rats, we generated several lines of the transgenic rats carrying the tetracycline-controlled transactivator (tTA gene. Using a vigorous, ubiquitous promoter to drive the tTA transgene, we obtained widespread expression of tTA in various tissues. Expression of tTA was sufficient to strongly activate its reporter gene, but was below the toxicity threshold. We examined the dynamics of Doxycycline (Dox-regulated gene expression in transgenic rats. In the two transmittable lines, tTA-mediated activation of the reporter gene was fully subject to regulation by Dox. Dox dose-dependently suppressed tTA-activated gene expression. The washout time for the effects of Dox was dose-dependent. We tested a complex regime of Dox administration to determine the optimal effectiveness and washout duration. Dox was administered at a high dose (500 μg/ml in drinking water for two days to reach the effective concentration, and then was given at a low dose (20 μg/ml to maintain effectiveness. This regimen of Dox administration can achieve a quick switch between ON and OFF statuses of tTA-activated gene expression. In addition, administration of Dox to pregnant rats fully suppressed postnatal tTA-activated gene expression in their offspring. Sufficient levels of Dox are present in mother's milk to produce maximal efficacy in nursing neonates. Administration of Dox to pregnant or nursing rats can provide a continual suppression of tTA-dependent gene expression during embryonic and postnatal development. The tTA transgenic rat allows for inducible and reversible gene expression in the rat; this important tool will be valuable in the development of genetic rat models of human diseases.

  20. Developing tTA transgenic rats for inducible and reversible gene expression.

    Zhou, Hongxia; Huang, Cao; Yang, Min; Landel, Carlisle P; Xia, Pedro Yuxing; Liu, Yong-Jian; Xia, Xu Gang

    2009-01-01

    To develop transgenic lines for conditional expression of desired genes in rats, we generated several lines of the transgenic rats carrying the tetracycline-controlled transactivator (tTA) gene. Using a vigorous, ubiquitous promoter to drive the tTA transgene, we obtained widespread expression of tTA in various tissues. Expression of tTA was sufficient to strongly activate its reporter gene, but was below the toxicity threshold. We examined the dynamics of Doxycycline (Dox)-regulated gene expression in transgenic rats. In the two transmittable lines, tTA-mediated activation of the reporter gene was fully subject to regulation by Dox. Dox dose-dependently suppressed tTA-activated gene expression. The washout time for the effects of Dox was dose-dependent. We tested a complex regime of Dox administration to determine the optimal effectiveness and washout duration. Dox was administered at a high dose (500 microg/ml in drinking water) for two days to reach the effective concentration, and then was given at a low dose (20 microg/ml) to maintain effectiveness. This regimen of Dox administration can achieve a quick switch between ON and OFF statuses of tTA-activated gene expression. In addition, administration of Dox to pregnant rats fully suppressed postnatal tTA-activated gene expression in their offspring. Sufficient levels of Dox are present in mother's milk to produce maximal efficacy in nursing neonates. Administration of Dox to pregnant or nursing rats can provide a continual suppression of tTA-dependent gene expression during embryonic and postnatal development. The tTA transgenic rat allows for inducible and reversible gene expression in the rat; this important tool will be valuable in the development of genetic rat models of human diseases. PMID:19214245

  1. Tissue-specific expression of the rat beta-casein gene in transgenic mice.

    Lee, K. F.; DeMayo, F J; Atiee, S H; Rosen, J. M.

    1988-01-01

    The rat beta-casein gene is a member of a small gene family, encoding the principal milk proteins. In order to understand the mechanisms by which its stage- and tissue-specific expression are regulated, initially, a 14 kb genomic clone containing the entire 7.5 kb rat beta-casein gene with 3.5 kb of 5' and 3.0 kb of 3' flanking DNA was microinjected into the germline of mice. Eight F0 transgenic mice were generated with copy numbers ranging from 1-10; five transmitted the transgene to their o...

  2. Differential regulation of rat beta-casein-chloramphenicol acetyltransferase fusion gene expression in transgenic mice.

    Lee, K. F.; Atiee, S H; Rosen, J. M.

    1989-01-01

    Previous studies in our laboratory have demonstrated the mammary-specific expression of the entire rat beta-casein gene with 3.5 kilobases (kb) of 5' and 3.0 kb of 3' DNA in transgenic mice (Lee et al., Nucleic Acids Res. 16:1027-1041, 1988). In an attempt to localize sequences that dictate this specificity, lines of transgenic mice carrying two different rat beta-casein promoter-bacterial chloramphenicol acetyltransferase (cat) fusion genes have been established. Twenty and eight lines of tr...

  3. Expression of the Mu Opioid Receptor in the Human Immunodeficiency Virus Type 1 Transgenic Rat Model▿

    Chang, Sulie L.; Beltran, Jose A.; SWARUP, SHILPA

    2007-01-01

    Opioids, via the mu opioid receptor (MOR), can exacerbate bacterial infections and the immunopathogenesis of human immunodeficiency virus type 1 (HIV-1) infection. Recently, an HIV-1 transgenic (HIV-1Tg) rat model containing circulating HIV-1 gp120 was created. Using real-time reverse transcription-PCR, we found that MOR mRNA levels were significantly higher in the peritoneal macrophages of the HIV-1Tg rat than those in control animals. Lipopolysaccharide, a bacterial endotoxin, induced secre...

  4. Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease

    Alexis Faure; Brown, Bruce L.; Nguyen, Hoa P.; Stephan Von Horsten

    2013-01-01

    Huntington's disease (HD) is characterized by triad of motor, cognitive, and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats), evidence suggest emotional alterations at the symptomatic stage along with neuro...

  5. A new transgenic rat model of of hepatic steatosis and the metabolic syndrome

    Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Qi, N.; Wang, J.; Kazdová, L.; Pravenec, Michal; Kurtz, T. W.

    Elsevier. Roč. 6, č. 1 (2005), s. 46-46. ISSN 1567-5688. [Congress of the European Atherosclerosis Society /75./. 23.04.2005-26.04.2005, Prague] Institutional research plan: CEZ:AV0Z50110509 Keywords : SREBP1A transgenic * rat * metabolic syndrome Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  6. New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein.

    Garcia Diaz, Ana Isabel; Moyon, Ben; Coan, Philip M; Alfazema, Neza; Venda, Lara; Woollard, Kevin; Aitman, Tim

    2016-04-01

    The Wistar Kyoto (WKY) rat and the spontaneously hypertensive (SHR) rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN) and metabolic syndrome, respectively. Novel transgenic (Tg) strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP) under the rat elongation factor 1 alpha (EF1a) promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminaryin vitroandin vivoimaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades. PMID:26769799

  7. New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein

    Ana Isabel Garcia Diaz

    2016-04-01

    Full Text Available The Wistar Kyoto (WKY rat and the spontaneously hypertensive (SHR rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN and metabolic syndrome, respectively. Novel transgenic (Tg strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP under the rat elongation factor 1 alpha (EF1a promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminary in vitro and in vivo imaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades.

  8. Neurobehavioral Alterations in HIV-1 Transgenic Rats: Evidence for Dopaminergic Dysfunction

    Moran, L. M.; Booze, R.M.; Webb, K. M.; Mactutus, C. F.

    2012-01-01

    Clinical studies have provided evidence that the progression of HIV-1-associated neurocognitive disorders (HAND) involves alterations in dopamine (DA) systems. Drugs of abuse that act on the brain DA system, such as cocaine (Coc), may exacerbate HIV-1 infection and consequent behavioral and neurological manifestations. In the present study, we used the HIV-1 transgenic (Tg) rat, which constitutively expresses 7 of the 9 HIV-1 genes, to assess potential DA system alterations in three behaviora...

  9. Chronic alcohol ingestion exacerbates skeletal muscle myopathy in HIV-1 transgenic rats

    Bratina Margaux A

    2011-08-01

    Full Text Available Abstract Background Separately, chronic alcohol ingestion and HIV-1 infection are associated with severe skeletal muscle derangements, including atrophy and wasting, weakness, and fatigue. One prospective cohort study reported that 41% of HIV-infected patients met the criteria for alcoholism, however; few reports exist on the co-morbid effects of these two disease processes on skeletal muscle homeostasis. Thus, we analyzed the atrophic effects of chronic alcohol ingestion in HIV-1 transgenic rats and identified alterations to several catabolic and anabolic factors. Findings Relative plantaris mass, total protein content, and fiber cross-sectional area were reduced in each experimental group compared to healthy, control-fed rats. Alcohol abuse further reduced plantaris fiber area in HIV-1 transgenic rats. Consistent with previous reports, gene levels of myostatin and its receptor activin IIB were not increased in HIV-1 transgenic rat muscle. However, myostatin and activin IIB were induced in healthy and HIV-1 transgenic rats fed alcohol for 12 weeks. Catabolic signaling factors such as TGFβ1, TNFα, and phospho-p38/total-p38 were increased in all groups compared to controls. There was no effect on IL-6, leukemia inhibitory factor (LIF, cardiotrophin-1 (CT-1, or ciliary neurotrophic factor (CNTF in control-fed, transgenic rats. However, the co-morbidity of chronic alcohol abuse and HIV-1-related protein expression decreased expression of the two anabolic factors, CT-1 and CNTF. Conclusions Consistent with previous reports, alcohol abuse accentuated skeletal muscle atrophy in an animal model of HIV/AIDS. While some catabolic pathways known to drive alcoholic or HIV-1-associated myopathies were also elevated in this co-morbid model (e.g., TGFβ1, consistent expression patterns were not apparent. Thus, specific alterations to signaling mechanisms such as the induction of the myostatin/activin IIB system or reductions in growth factor signaling via

  10. Immune Activation, Viral Gene Product Expression and Neurotoxicity in the HIV-1 Transgenic Rat

    Royal, Walter; Zhang, Li; Guo, Ming; Jones, Odell; Davis, Harry; Bryant, Joseph L.

    2012-01-01

    The HIV-1 transgenic (TG) rat has been shown to be a useful model of nervous system disease that occurs in human HIV-1 infection. Studies were, therefore, performed to examine characteristics of the immune response in the periphery and brain of the animals and expression of factors in the nervous system that might be associated with neurotoxicity. Activated splenocytes from wild-type (WT) and TG rats were stimulated with either CD3/CD28 or with lipopolysaccharide (LPS) and examined for prolif...

  11. Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT).

    Kaneko, Ryosuke; Sato, Atsuko; Hamada, Shun; Yagi, Takeshi; Ohsawa, Ichiro; Ohtsuki, Mamitaro; Kobayashi, Eiji; Hirabayashi, Masumi; Murakami, Takashi

    2016-08-01

    Childhood-onset dermatitis is one of the most common skin disorders in children. Although various mouse models that mirror aspects of dermatitis have become available, there is still a need for an animal model that develops dermatitis in childhood and is more suitable for performing tissue transplantation experiments. There is emerging evidence that peripheral blood T lymphocytes from patients with dermatitis have significantly increased telomerase activity. Here, we developed telomerase reverse transcriptase (TERT)-expressing transgenic (Tg) rats that spontaneously developed eczematous skin inflammation in childhood. Newborn TERT-Tg rats developed visible dermatitis in 56 % of cases, and the skin lesions microscopically showed spongiosis and acanthosis with infiltration of lymphocytes, eosinophils and mast cells. TERT-Tg rats with dermatitis exhibited increased CD4 (2.5-fold) and CD8 (fivefold) T cell numbers compared with dermatitis-free TERT-Tg rats. Stronger TERT activity was observed in the peripheral lymphocytes of dermatitis-positive TERT-Tg rats than those of dermatitis-free TERT-Tg rats. RT-PCR analysis revealed that IL-4 was markedly elevated in the spleen of dermatitis-positive TERT-Tg rats, and that interferon-gamma was increased in the dermatitis lesions. Moreover, skin grafting of TERT-Tg rats with dermatitis onto T cell-deficient nude rats demonstrated that the inflamed skin lesions could not be maintained. Taken together, the results suggest that TERT activation in T lymphocytes is one of the potential predisposing factors for dermatitis. Moreover, our results demonstrated that the TERT-Tg rats mirror aspects of human childhood-onset dermatitis and that these animals represent a potential animal model system for studying childhood-onset dermatitis. PMID:26885830

  12. Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling

    Kornélia Szebényi; András Füredi; Orsolya Kolacsek; Enikő Pergel; Zsuzsanna Bősze; Balázs Bender; Péter Vajdovich; József Tóvári; László Homolya; Gergely Szakács; László Héja; Ágnes Enyedi; Balázs Sarkadi; Ágota Apáti; Orbán, Tamás I.

    2015-01-01

    In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct, an...

  13. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats

    Harry Gaylia; Kraft Andrew; Chen Mei; Greenstein Dede; Kellom Matthew; Kim Hyung-Wook; Rao Jagadeesh; Rapoport Stanley; Basselin Mireille

    2011-01-01

    Abstract Background Cognitive impairment has been reported in human immune deficiency virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats. This impairment has been linked to neuroinflammation, disturbed brain arachidonic acid (AA) metabolism, and synapto-dendritic injury. We recently reported upregulated brain AA metabolism in 7- to 9-month-old HIV-1 Tg rats. We hypothesized that these HIV-1 Tg rats also would show upregulated brain inflammatory and AA cascade markers...

  14. Transgenic approach to express the channelrhodopsin 2 gene in arginine vasopressin neurons of rats.

    Ishii, Masahiro; Hashimoto, Hirofumi; Ohkubo, Jun-Ichi; Ohbuchi, Toyoaki; Saito, Takeshi; Maruyama, Takashi; Yoshimura, Mitsuhiro; Yamamoto, Yukiyo; Kusuhara, Koichi; Ueta, Yoichi

    2016-09-01

    Optogenetics provides a powerful tool to regulate neuronal activity by light-sensitive ion channels such as channelrhodopsin 2 (ChR2). Arginine vasopressin (AVP; also known as the anti-diuretic hormone) is a multifunctional hormone which is synthesized in the magnocellular neurosecretory cells (MNCs) of the hypothalamus. Here, we have generated a transgenic rat that expresses an AVP-ChR2-enhanced green fluorescent protein (eGFP) fusion gene in the MNCs of the hypothalamus. The eGFP fluorescence that indicates the expression of ChR2-eGFP was observed in the supraoptic nucleus (SON) and in the magnocellular division of the paraventricular nucleus (PVN) that is known to contain AVP-secreting neurons. The eGFP fluorescence intensities in those nuclei and posterior pituitary were markedly increased after chronic salt loading (2% NaCl in drinking water for 5days). ChR2-eGFP was localized mainly in the membrane of AVP-positive MNCs. Whole-cell patch-clamp recordings were performed from single MNCs isolated from the SON of the transgenic rats, and blue light evoked repetitive action potentials. Our work provides for the first time an optogenetic approach to selectively activate AVP neurons in the rat. PMID:27493075

  15. Light-evoked Somatosensory Perception of Transgenic Rats That Express Channelrhodopsin-2 in Dorsal Root Ganglion Cells

    Zhi-Gang Ji; Shin Ito; Tatsuya Honjoh; Hiroyuki Ohta; Toru Ishizuka; Yugo Fukazawa; Hiromu Yawo

    2012-01-01

    In vertebrate somatosensory systems, each mode of touch-pressure, temperature or pain is sensed by sensory endings of different dorsal root ganglion (DRG) neurons, which conducted to the specific cortical loci as nerve impulses. Therefore, direct electrical stimulation of the peripheral nerve endings causes an erroneous sensation to be conducted by the nerve. We have recently generated several transgenic lines of rat in which channelrhodopsin-2 (ChR2) transgene is driven by the Thy-1.2 promot...

  16. Effect of HIV-1-related protein expression on cardiac and skeletal muscles from transgenic rats

    Guidot David M

    2008-04-01

    Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 infection and the consequent acquired immunodeficiency syndrome (AIDS has protean manifestations, including muscle wasting and cardiomyopathy, which contribute to its high morbidity. The pathogenesis of these myopathies remains partially understood, and may include nutritional deficiencies, biochemical abnormalities, inflammation, and other mechanisms due to viral infection and replication. Growing evidence has suggested that HIV-1-related proteins expressed by the host in response to viral infection, including Tat and gp120, may also be involved in the pathophysiology of AIDS, particularly in cells or tissues that are not directly infected with HIV-1. To explore the potentially independent effects of HIV-1-related proteins on heart and skeletal muscles, we used a transgenic rat model that expresses several HIV-1-related proteins (e.g., Tat, gp120, and Nef. Outcome measures included basic heart and skeletal muscle morphology, glutathione metabolism and oxidative stress, and gene expressions of atrogin-1, muscle ring finger protein-1 (MuRF-1 and Transforming Growth Factor-β1 (TGFβ1, three factors associated with muscle catabolism. Results Consistent with HIV-1 associated myopathies in humans, HIV-1 transgenic rats had increased relative heart masses, decreased relative masses of soleus, plantaris and gastrocnemius muscles, and decreased total and myosin heavy chain type-specific plantaris muscle fiber areas. In both tissues, the levels of cystine (Cyss, the oxidized form of the anti-oxidant cysteine (Cys, and Cyss:Cys ratios were significantly elevated, and cardiac tissue from HIV-1 transgenic rats had altered glutathione metabolism, all reflective of significant oxidative stress. In HIV-1 transgenic rat hearts, MuRF-1 gene expression was increased. Further, HIV-1-related protein expression also increased atrogin-1 (~14- and ~3-fold and TGFβ1 (~5-fold and ~3-fold in heart and

  17. Endotoxin-Mediated Downregulation of Hepatic Drug Transporters in HIV-1 Transgenic Rats.

    Ghoneim, Ragia H; Piquette-Miller, Micheline

    2016-05-01

    Altered expression of drug transporters and metabolic enzymes is known to occur in infection-induced inflammation. We hypothesize that in human immunodeficiency virus (HIV)-infected individuals, further alteration could occur as a result of augmented inflammation. The HIV-1 transgenic (Tg) rat is used to simulate HIV pathologies associated with the presence of HIV viral proteins. Therefore, the objective of this study was to examine the effect of endotoxin administration on the gene expression of drug transporters in the liver of HIV-Tg rats. Male and female HIV-Tg and wild-type (WT) littermates were injected with 5 mg/kg endotoxin or saline (n= 7-9/group). Eighteen hours later, rats were euthanized and tissues were collected. Quantitative real-time polymerase chain reaction and Western blot analysis were used to measure hepatic gene and protein expression, respectively, and enzyme-linked immunosorbent assay was used to measure serum cytokine levels. Although an augmented inflammatory response was seen in HIV-Tg rats, similar endotoxin- mediated downregulation of Abcb1a, Abcc2, Abcg2, Abcb11, Slco1a1, Slco1a2, Slco1b2, Slc10a1, Slc22a1, Cyp3a2, and Cyp3a9 gene expression was seen in the HIV-Tg and WT groups. A significantly greater endotoxin- mediated downregulation of Ent1/Slc29a1 was seen in female HIV-Tg rats. Basal expression of inflammatory mediators was not altered in the HIV-Tg rat; likewise, the basal expression of most transporters was not significantly different between HIV-Tg and WT rats. Our findings suggest that hepatobiliary clearances of endogenous and exogenous substrates are altered in the HIV-Tg rat after endotoxin exposure. This is of particular importance because HIV-infected individuals frequently present with bacterial or viral infections, which are a potential source for drug-disease interactions. PMID:26977098

  18. Effect of Cocaine on Pulmonary Vascular Remodeling and Hemodynamics in Human Immunodeficiency Virus-Transgenic Rats.

    Dalvi, Pranjali; Spikes, Leslie; Allen, Julie; Gupta, Vijayalaxmi G; Sharma, Himanshu; Gillcrist, Marion; Montes de Oca, Jamison; O'Brien-Ladner, Amy; Dhillon, Navneet K

    2016-08-01

    Human immunodeficiency virus (HIV)-related pulmonary arterial hypertension has been found to be more prevalent in intravenous drug users. Our earlier cell-culture findings reported down-regulation of bone morphogenetic protein receptors (BMPRs) in combination with enhanced proliferation of human pulmonary arterial smooth muscle cells (PASMCs) in the presence of HIV-Trans-activator of transcription (Tat) and cocaine compared with either treatment alone. Here, we report physiologic evidence of significant increases in mean pulmonary arterial pressure in HIV-transgenic (Tg) rats intraperitoneally administered 40 mg/kg body weight cocaine (HIV-cocaine group) once daily for 21 days when compared with HIV-Tg rats given saline (HIV group) or wild-type (WT) Fischer 334 rats treated with (WT-cocaine group) and without cocaine (WT group). In addition, right ventricle systolic pressure was also found to be significantly higher in the HIV-cocaine rats compared with the WT group. Significant down-regulation in protein expression of BMPR-2 and BMPR-1B was observed in total lung extract from HIV-cocaine rats compared with the other three groups. Furthermore, the PASMCs isolated from HIV-cocaine rats demonstrated a higher level of proliferation and lower levels of apoptosis compared with cells isolated from other rat groups. Interestingly, corroborating our earlier cell-culture findings, we observed higher expression of BMPR-2 and BMPR-1B messenger RNA and significantly lower levels of BMPR-2 and BMPR-1B protein in HIV-cocaine PASMCs compared with cells isolated from all other groups. In conclusion, our findings support an additive effect of cocaine and HIV on smooth muscle dysfunction, resulting in enhanced pulmonary vascular remodeling with associated elevation of mean pulmonary arterial pressure and right ventricle systolic pressure in HIV-Tg rats exposed to cocaine. PMID:26820592

  19. Generation of a novel transgenic rat model for tracing extracellular vesicles in body fluids.

    Yoshimura, Aya; Kawamata, Masaki; Yoshioka, Yusuke; Katsuda, Takeshi; Kikuchi, Hisae; Nagai, Yoshitaka; Adachi, Naoki; Numakawa, Tadahiro; Kunugi, Hiroshi; Ochiya, Takahiro; Tamai, Yoshitaka

    2016-01-01

    Extracellular vesicles (EVs) play an important role in the transfer of biomolecules between cells. To elucidate the intercellular transfer fate of EVs in vivo, we generated a new transgenic (Tg) rat model using green fluorescent protein (GFP)-tagged human CD63. CD63 protein is highly enriched on EV membranes via trafficking into late endosomes and is often used as an EV marker. The new Tg rat line in which human CD63-GFP is under control of the CAG promoter exhibited high expression of GFP in various body tissues. Exogenous human CD63-GFP was detected on EVs isolated from three body fluids of the Tg rats: blood serum, breast milk and amniotic fluid. In vitro culture allowed transfer of serum-derived CD63-GFP EVs into recipient rat embryonic fibroblasts, where the EVs localized in endocytic organelles. These results suggested that this Tg rat model should provide significant information for understanding the intercellular transfer and/or mother-child transfer of EVs in vivo. PMID:27539050

  20. Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats

    Haller Hermann

    2002-01-01

    Full Text Available Abstract Background We are investigating a double transgenic rat (dTGR model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1 are expressed early on the endothelium, while the corresponding ligands are found on circulating leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1, iNOS and Tissue Factor expression. Furthermore we show evidence that Ang II causes the upregulation of NF-kB in our model. Methods We started PDTC-treatment on four weeks old dTGR (200 mg/kg sc and age-matched SD rats.. Blood-pressure- and albuminuria- measurements were monitored during the treatement period (four weeks. The seven weeks old animals were killed, hearts and kidneys were isolated and used for immunohistochemical-and electromobility shift assay analsis. Results Chronic treatment with the antioxidant PDTC decreased blood pressure (162 ± 8 vs. 190 ± 7 mm Hg, p = 0.02. Cardiac hypertrophy index was significantly reduced (4.90 ± 0.1 vs. 5.77 ± 0.1 mg/g, p Conclusion Our data show that inhibition of NF-κB by PDTC markedly reduces inflammation, iNOS expression in the dTGR most likely leading to decreased cytotoxicity, and cell proliferation. Thus, NF-κB activation plays an important role in ANG II-induced end-organ damage.

  1. HIV-1 transgenic rats display alterations in immunophenotype and cellular responses associated with aging.

    Susan J Abbondanzo

    Full Text Available Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in immune response changes, alterations in immunological phenotypes, and ultimately increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV-1 disease, particularly in aging individuals, the HIV-1 transgenic (HIV-1Tg rat model was utilized. HIV-1Tg rats were challenged with lipopolysaccharide (LPS to determine immunological alterations during the aging process. LPS is known to cause an imbalance in cytokine and chemokine release, and provides a method to identify changes in immune responses to bacterial infection in an HIV animal model. An immune profile and accompanying cellular consequences as well as changes in inflammatory cytokine and chemokine release related to age and genotype were assessed in HIV-1Tg rats. The percentage of T cells decreased with age, particularly T cytotoxic cells, whereas T helper cells increased with age. Neutrophils and monocytes increased in HIV-1Tg rats during maturation compared to age-matched F344 control rats. Aging HIV-1Tg rats displayed a significant increase in the pro-inflammatory cytokines, IL-6 and TNF-α, along with an increase in the chemokine, KC/GRO, in comparison to age-matched controls. Our data indicate that immunophenotype and immune responses can change during aging in HIV-positive individuals. This information could be important in determining the most beneficial age-dependent therapeutic treatment for HIV patients.

  2. Rescue of photoreceptor degeneration by curcumin in transgenic rats with P23H rhodopsin mutation.

    Vidyullatha Vasireddy

    Full Text Available The P23H mutation in the rhodopsin gene causes rhodopsin misfolding, altered trafficking and formation of insoluble aggregates leading to photoreceptor degeneration and autosomal dominant retinitis pigmentosa (RP. There are no effective therapies to treat this condition. Compounds that enhance dissociation of protein aggregates may be of value in developing new treatments for such diseases. Anti-protein aggregating activity of curcumin has been reported earlier. In this study we present that treatment of COS-7 cells expressing mutant rhodopsin with curcumin results in dissociation of mutant protein aggregates and decreases endoplasmic reticulum stress. Furthermore we demonstrate that administration of curcumin to P23H-rhodopsin transgenic rats improves retinal morphology, physiology, gene expression and localization of rhodopsin. Our findings indicate that supplementation of curcumin improves retinal structure and function in P23H-rhodopsin transgenic rats. This data also suggest that curcumin may serve as a potential therapeutic agent in treating RP due to the P23H rhodopsin mutation and perhaps other degenerative diseases caused by protein trafficking defects.

  3. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

    Evans, David M; Spencer, Chris C.A.; Pointon, Jennifer J.; Su, Zhan; Harvey, David; Kochan, Grazyna; Oppermann, Udo; Dilthey, Alexander; Pirinen, Matti; Stone, Millicent A.; Appleton, Louise; Moutsianas, Loukas; Leslie, Stephen; Wordsworth, Tom; Kenna, Tony J.

    2011-01-01

    Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBRTNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10−8 in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all...

  4. Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease

    Alexis Faure

    2013-09-01

    Full Text Available Huntington’s disease (HD is characterized by triad of motor, cognitive and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats, evidence suggest emotional alterations at the symptomatic stage along with neuropathology of the central nucleus of amygdala (CE. Studies in humans and animals demonstrate that emotion can modulate time perception. The impact of emotion on time perception has never been tested in HD, nor is it known if that impact could be part of the presymptomatic emotional phenotype of the pathology. The aim of this paper was to characterize the effect of emotion on temporal discrimination in presymptomatic tgHD animals. In the first experiment, we characterized the acute effect of an emotion (fear conditioned stimulus on temporal discrimination using a bisection procedure, and tested its dependency upon an intact central amygdala. The second experiment was aimed at comparing presymptomatic homozygous transgenic animals at 7-months of age and their wild-type littermates (WT in their performance on the modulation of temporal discrimination by emotion. Our principal findings show that (1 a fear cue produces a short-lived decrease of temporal precision after its termination, and (2 animals with medial CE lesion and presymptomatic tgHD animals demonstrate an alteration of this emotion-evoked temporal distortion. The results contribute to our knowledge about the presymptomatic phenotype of this HD rat model, showing susceptibility to emotion that may be related to dysfunction of the central nucleus of amygdala.

  5. Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease.

    Faure, Alexis; Es-Seddiqi, Mouna; Brown, Bruce L; Nguyen, Hoa P; Riess, Olaf; von Hörsten, Stephan; Le Blanc, Pascale; Desvignes, Nathalie; Bozon, Bruno; El Massioui, Nicole; Doyère, Valérie

    2013-01-01

    Huntington's disease (HD) is characterized by triad of motor, cognitive, and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats), evidence suggest emotional alterations at the symptomatic stage along with neuropathology of the central nucleus of amygdala (CE). Studies in humans and animals demonstrate that emotion can modulate time perception. The impact of emotion on time perception has never been tested in HD, nor is it known if that impact could be part of the presymptomatic emotional phenotype of the pathology. The aim of this paper was to characterize the effect of emotion on temporal discrimination in presymptomatic tgHD animals. In the first experiment, we characterized the acute effect of an emotion (fear) conditioned stimulus on temporal discrimination using a bisection procedure, and tested its dependency upon an intact central amygdala. The second experiment was aimed at comparing presymptomatic homozygous transgenic animals at 7-months of age and their wild-type littermates (WT) in their performance on the modulation of temporal discrimination by emotion. Our principal findings show that (1) a fear cue produces a short-lived decrease of temporal precision after its termination, and (2) animals with medial CE lesion and presymptomatic tgHD animals demonstrate an alteration of this emotion-evoked temporal distortion. The results contribute to our knowledge about the presymptomatic phenotype of this HD rat model, showing susceptibility to emotion that may be related to dysfunction of the central nucleus of amygdala. PMID:24133419

  6. Mutagenesis by asbestos in the lung of lambda-lacI transgenic rats.

    Topinka, J; Loli, P; Georgiadis, P; Dusinská, M; Hurbánková, M; Kováciková, Z; Volkovová, K; Kazimírová, A; Barancoková, M; Tatrai, E; Oesterle, D; Wolff, T; Kyrtopoulos, S A

    2004-09-01

    In order to get more insight into the mechanism of asbestos-related lung cancer, the mutagenic potential of asbestos was examined in vivo in rat lung. Groups of five transgenic lambda-lacI (Big Blue) rats were intratracheally instilled with single doses of 1 or 2mg, or with four weekly doses of 2mg, per animal of the amosite asbestos. Sixteen weeks after instillation, the mutation frequency was found to be increased in lung DNA by 2-fold at doses of 2 mg (P = 0.035) and of 4 x 2 mg (P = 0.007) amosite. No significant changes were observed after 4 weeks of exposure. In separate experiments, wild-type F344 rats were treated by the same regimen as described above and markers of inflammation, genotoxicity, cell proliferation and lung tissue damage were analysed. Our results indicate a weak but persistent inflammation and cell proliferation which possibly plays a major role in the observed mutagenic effect. PMID:15288534

  7. Neurobehavioral alterations in HIV-1 transgenic rats: evidence for dopaminergic dysfunction.

    Moran, L M; Booze, R M; Webb, K M; Mactutus, C F

    2013-01-01

    Clinical studies have provided evidence that the progression of HIV-1-associated neurocognitive disorders (HAND) involves alterations in dopamine (DA) systems. Drugs of abuse that act on the brain DA system, such as cocaine (Coc), may exacerbate HIV-1 infection and consequent behavioral and neurological manifestations. In the present study, we used the HIV-1 transgenic (Tg) rat, which constitutively expresses 7 of the 9 HIV-1 genes, to assess potential DA system alterations in three behavioral assays: prepulse inhibition (PPI) of the auditory startle response (ASR), novelty and habituation/retention, and sensitization to Coc across repeated administration. Adult female Sprague-Dawley rats were tested in each experiment. The HIV-1 Tg animals were hyperreactive to auditory startle stimuli and displayed a leftward shift in the temporal window for maximal PPI, suggesting an alteration in sensorimotor gating. All animals displayed an initial robust locomotor response to a novel environment which dissipated with repeated testing; however, the HIV-1 Tg rats, relative to controls, consistently showed a weaker novelty response across monthly-spaced assessments. The HIV-1 Tg animals also showed decreased intrasession habituation of motor activity across 3-day periods that emerged across monthly-spaced locomotor activity sessions; a pattern consistent with impaired long-term episodic memory. Furthermore, the HIV-1 Tg group displayed differential cocaine-induced sensitization, observed both in initiation across the 10-day cocaine treatment, and in expression following a cocaine rechallenge after a 7-day abstinence. Collectively, the present data implicate that the non-infectious HIV-1 Tg rat, which resembles the complete suppression of infection in HIV-1 positive individuals under CART, displays sustained, if not permanent, alterations in the brain DA system. PMID:23063600

  8. Food-anticipatory activity and liver per1-luc activity in diabetic transgenic rats

    Davidson, Alec J.; Stokkan, Karl-Arne; Yamazaki, Shin; Menaker, Michael

    2002-01-01

    The mammalian Per1 gene is an important component of the core cellular clock mechanism responsible for circadian rhythms. The rodent liver and other tissues rhythmically express Per1 in vitro but typically damp out within a few cycles. In the liver, the peak of this rhythm occurs in the late subjective night in an ad lib-fed rat, but will show a large phase advance in response to restricted availability of food during the day. The relationship between this shift in the liver clock and food-anticipatory activity (FAA), the circadian behavior entrained by daily feeding, is currently unknown. Insulin is released during feeding in mammals and could serve as an entraining signal to the liver. To test the role of insulin in the shift in liver Per1 expression and the generation of FAA, per-luciferase transgenic rats were made diabetic with a single injection of streptozotocine. Following 1 week of restricted feeding and locomotor activity monitoring, liver was collected for per-luc recording. In two separate experiments, FAA emerged and liver Per1 phase-shifted in response to daytime 8-h food restriction. The results rule out insulin as a necessary component of this system.

  9. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    Atrayee Banerjee

    Full Text Available The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH (3.5 g/kg/dose oral gavages at 12-h intervals or dextrose (Control. Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4, leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1 were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART, are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  10. Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer's disease

    Galeano, Pablo; Martino Adami, Pamela V.; Do Carmo, Sonia; Blanco, Eduardo; Rotondaro, Cecilia; Capani, Francisco; Castaño, Eduardo M; Cuello, A. Claudio; Morelli, Laura

    2014-01-01

    Intraneuronal accumulation of amyloid β (iAβ) has been linked to mild cognitive impairment that may precede Alzheimer's disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg(+/-)) rat. The characterization of the behavioral phenotypes in this animal model could provide a baseline of efficacy for earlier therapeutic interventions. The aim of the present study was to undertake a longitudinal study of...

  11. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats

    Hag, Anne Mette Fisker; Kristoffersen, Ulrik Sloth; Pedersen, Sune Folke;

    2009-01-01

    endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in HIV-1......-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease....

  12. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

    Malínská, H.; Oliyarnyk, O.; Škop, V.; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, L.; Pravenec, Michal

    2016-01-01

    Roč. 11, č. 3 (2016), e0150924. E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : inflammation * spontaneously hypertensive rat * transgenic * C-reactive protein * dicarbonyl stress * metformin Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.234, year: 2014

  13. Rosuvastatin ameliorates inflammation, renal fat accumulation, and kidney injury in transgenic spontaneously hypertensive rats expressing human C-reactive protein

    Šilhavý, Jan; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Mancini, M.; Pravenec, Michal

    2015-01-01

    Roč. 64, č. 3 (2015), s. 295-301. ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : rosuvastatin * kidney damage * CRP * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.293, year: 2014

  14. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats.

    Anne Mette Fisker Hag

    Full Text Available BACKGROUND: Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1, vascular cell adhesion molecule-1 (VCAM-1, and intercellular adhesion molecule-1 (ICAM-1 in HIV-1 transgenic (HIV-1Tg rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease.

  15. S100A1 transgenic treatment of acute heart failure causes proteomic changes in rats

    Guo, Yichen; Cui, Lianqun; Jiang, Shiliang; Wang, Dongmei; Jiang, Shu; Xie, Chen; Jia, Yanping

    2016-01-01

    S100 Ca2+-binding protein A1 (S100A1) is an important regulator of myocardial contractility. The aim of the present study was to identify the underlying mechanisms of S100A1 activity via profiling the protein expression in rats administered with an S100A1 adenovirus (Ad-S100A1-EGFP) following acute myocardial infarction (AMI). LTQ OrbiTrap mass spectrometry was used to profile the protein expression in the Ad-S100A1-EGFP and control groups post-AMI. Using Protein Analysis Through Evolutionary Relationships (PANTHER) analysis, 134 energy metabolism-associated proteins, which comprised 20 carbohydrate metabolism-associated and 27 lipid metabolism associated proteins, were identified as differentially expressed in the Ad-S100A1-EGFP hearts compared with controls. The majority of the differentially expressed proteins identified were important enzymes involved in energy metabolism. The present study identified 12 Ca2+-binding proteins and 22 cytoskeletal proteins. The majority of the proteins expressed in the Ad-S100A1-EGFP group were upregulated compared with the control group. These results were further validated using western blot analysis. Following AMI, Ca2+ is crucial for the recovery of myocardial function in S100A1 transgenic rats as indicated by the upregulation of proteins associated with energy metabolism and Ca2+-binding. Thus, the current study ascertained that energy production and contractile ability were enhanced after AMI in the ventricular myocardium of the Ad-S100A1-EGFP group. PMID:27357314

  16. Radiographic visualisation of seropositive rheumatoid arthritis in Carriers of HLA-B27

    Jurik, A.G.; Carvalho, A. de; Graudal, H.

    1987-07-01

    A group of 11 B27-positive, seropositive patients with rheumatoid arthritis was compared with 11 matched B27-negative seropositive patients. The radiographs of all limb joints, the sacroiliac joints, and the cervical spine were read blindly. Ten patients in each group were radiographed 2-6 times during observation periods of 3-13 years; one patient in each group was only examined once. The prevailing picture of both groups was that of progressive erosive rheumatoid arthritis, although two small differences were found: Erosions of the apophyseal joints of the cervical spine and slight periosteal new bone formation of the shoulder, hip, and knee regions occurred more often in the B27-positive than in the B27-negative group.

  17. Interplay between environmental factors, articular involvement, and HLA-B27 in patients with psoriatic arthritis.

    Scarpa, R.; DEL PUENTE A; di Girolamo, C; Della Valle, G.; E. Lubrano; Oriente, P

    1992-01-01

    Medical records of 138 patients with psoriatic arthritis and 138 with rheumatoid arthritis were reviewed for the occurrence of an environmental factor triggering arthritis. Twelve (9%) of the patients with psoriatic arthritis had had an acute disorder immediately preceding onset of arthritis (an operation in four cases, articular trauma in three, abortion in two, myocardial infarction, thrombophlebitis, and phosphoric ester intoxication in one case each). Peripheral arthritis occurred in all ...

  18. Comparison of HLA-B27 detection by flow cytometry and SSP-PCR and study on HLA-B27 subtypes%流式细胞术与 PCR-SSP 法检测 HLA-B27的比对及 HLA-B27亚型的研究

    白世杰; 托娅; 张保平; 王丽娟; 王雅菲

    2016-01-01

    Objective To investigate the application of flow cytometry (FCM ) and sequence‐specific primer polymerase chain reaction (PCR‐SSP) method in the detection of human leukocyte antigen‐B27 (HLA‐B27) and to observe the distribution of HLA‐B27 subtypes in the local region .Methods The HLA‐B27 level in 88 cases of sus‐pected ankylosing spondylitis (AS) was detected by FCM and PCR‐SSP .Results Among 88 cases of suspected AS , 82 cases were HLA‐B27 positive and 6 cases were HLA‐B27 negative by FCM ,the positive rate was 93 .2% ;whereas 83 cases were HLA‐B27 positive and 5 cases were HLA‐B27 negative by PCR‐SSP ,the positive rate was 94 .3% .In the subtyping results ,41 cases were B * 2705 genotype ,accounting for 49 .4% ,37 cases were B * 2704 genotype ,ac‐counting for 44 .5% ,1 case was B * 2702 genotype ,accounting for 1 .2% ,4 cases were positive without distinguished genotype .Conclusion The Kappa consistency coefficient is 0 .905 ,the detection results of HLA‐B27 by PCR‐SSP and FCM have higher consistency .The susceptible HLA‐B27 allele subtypes are mainly HLA‐B * 2704 and HLA‐B *2705 .%目的:探讨流式细胞术(FCM )与序列特异性引物聚合酶链式反应(PCR‐SSP)在人类白细胞表面抗原‐B27(HLA‐B27)检测中的应用,并观察 HLA‐B27亚型在本地区的分布情况。方法采用 PCR‐SSP 和 FCM 检测88例疑似强直性脊柱炎(AS)患者 HLA‐B27。结果88例 AS 疑似患者中 FCM 法检测 HLA‐B27结果阳性82例,阴性6例,阳性率为93.2%;PCR‐SSP 法检测阳性83例、阴性5例、阳性率为94.3%。分型结果 B 倡2705型41例占49.4%;B 倡2704型37例占44.5%;B 倡2702型1例占1.2%;阳性但未分辨型别4例。结论 Kappa 一致性系数 K =0.905,PCR‐SSP 法与 FCM 检测 HLA‐B27结果具有较高的一致性。本地区易感 HLA‐B27等位基因亚型主要以 HLA‐B 倡2704和 HLA‐B 倡2705为主。

  19. Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer’s disease

    Pablo Galeano

    2014-09-01

    Full Text Available Intraneuronal accumulation of amyloid β (iAβ has been linked to mild cognitive impairment that may precede Alzheimer’s disease (AD onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg+/- rat. The characterization of the behavioral phenotypes in this animal model could provide a baseline of efficacy for earlier therapeutic interventions. The aim of the present study was to undertake a longitudinal study of Aβ accumulation and a comprehensive behavioral evaluation of this transgenic rat model. We assessed exploratory activity, anxiety-related behaviors, recognition memory, working memory, spatial learning and reference memory at 3, 6 and 12 months of age. In parallel, we measured Aβ by ELISA, Western blots and semiquantitative immunohistochemistry in hippocampal samples. SDS-soluble Aβ peptide accumulated at low levels (~9 pg/mg without differences among ages. However, Western blots showed SDS-resistant Aβ oligomers (~30 kDa at 6 and 12 months, but not at 3 months. When compared to wild-type (WT, male Tg+/- rats exhibited a spatial reference memory deficit in the Morris Water Maze (MWM as early as 3 months of age, which persisted at 6 and 12 months. In addition, Tg+/- rats displayed a working memory impairment in the Y-maze and higher anxiety levels in the Open Field (OF at 6 and 12 months of age, but not at 3 months. Exploratory activity in the OF was similar to that of WT at all time points. Spatial learning in the MWM and the recognition memory, as assessed by the Novel Object Recognition Test, were unimpaired at any time point. The data from the present study demonstrate that the hemizygous transgenic McGill-R-Thy1-APP rat has a wide array of behavioral and cognitive impairments from young adulthood to middle-age. The low Aβ burden and early emotional and cognitive deficits in this transgenic rat model supports its potential use for drug discovery

  20. Sustained and promoter dependent bone morphogenetic protein expression by rat mesenchymal stem cells after BMP-2 transgene electrotransfer

    E Ferreira

    2012-07-01

    Full Text Available Transplantation of mesenchymal stem cells (MSCs with electrotransferred bone morphogenetic protein-2 (BMP-2 transgene is an attractive therapeutic modality for the treatment of large bone defects: it provides both stem cells with the ability to form bone and an effective bone inducer while avoiding viral gene transfer. The objective of the present study was to determine the influence of the promoter driving the human BMP-2 gene on the level and duration of BMP-2 expression after transgene electrotransfer into rat MSCs. Cytomegalovirus, elongation factor-1α, glyceraldehyde 3-phosphate dehydrogenase, and beta-actin promoters resulted in a BMP-2 secretion rate increase of 11-, 78-, 66- and 36-fold over respective controls, respectively. In contrast, the osteocalcin promoter had predictable weak activity in undifferentiated MSCs but induced the strongest BMP-2 secretion rates in osteoblastically-differentiated MSCs. Regardless of the promoter driving the transgene, a plateau of maximal BMP-2 secretion persisted for at least 21 d after the hBMP-2 gene electrotransfer. The present study demonstrates the feasibility of gene electrotransfer for efficient BMP-2 transgene delivery into MSCs and for a three-week sustained BMP-2 expression. It also provides the first in vitro evidence for a safe alternative to viral methods that permit efficient BMP-2 gene delivery and expression in MSCs but raise safety concerns that are critical when considering clinical applications.

  1. Axonal diameter and density estimated with 7-Tesla hybrid diffusion imaging in transgenic Alzheimer rats

    Daianu, Madelaine; Jacobs, Russell E.; Town, Terrence; Thompson, Paul M.

    2016-03-01

    Diffusion-weighted MR imaging (DWI) is a powerful tool to study brain tissue microstructure. DWI is sensitive to subtle changes in the white matter (WM), and can provide insight into abnormal brain changes in diseases such as Alzheimer's disease (AD). In this study, we used 7-Tesla hybrid diffusion imaging (HYDI) to scan 3 transgenic rats (line TgF344-AD; that model the full clinico-pathological spectrum of the human disease) ex vivo at 10, 15 and 24 months. We acquired 300 DWI volumes across 5 q-sampling shells (b=1000, 3000, 4000, 8000, 12000 s/mm2). From the top three b-value shells with highest signal-to-noise ratios, we reconstructed markers of WM disease, including indices of axon density and diameter in the corpus callosum (CC) - directly quantifying processes that occur in AD. As expected, apparent anisotropy progressively decreased with age; there were also decreases in the intra- and extra-axonal MR signal along axons. Axonal diameters were larger in segments of the CC (splenium and body, but not genu), possibly indicating neuritic dystrophy - characterized by enlarged axons and dendrites as previously observed at the ultrastructural level (see Cohen et al., J. Neurosci. 2013). This was further supported by increases in MR signals trapped in glial cells, CSF and possibly other small compartments in WM structures. Finally, tractography detected fewer fibers in the CC at 10 versus 24 months of age. These novel findings offer great potential to provide technical and scientific insight into the biology of brain disease.

  2. Kisspeptin regulates gonadotropin-releasing hormone secretion in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats

    Haogang Xue; Chunying Yang; Xiaodong Ge; Weiqi Sun; Chun Li; Mingyu Qi

    2013-01-01

    Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kisspeptin antagonist peptide 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.

  3. Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression

    Thorsell, A.; Michalkiewicz, M.; Dumont, Y.; Quirion, R.; Caberlotto, L.; Rimondini, R.; Mathé, A. A.; Heilig, M.

    2000-01-01

    Exogenous neuropeptide Y (NPY) reduces experimental anxiety in a wide range of animal models. The generation of an NPY-transgenic rat has provided a unique model to examine the role of endogenous NPY in control of stress and anxiety-related behaviors using paradigms previously used by pharmacological studies. Locomotor activity and baseline behavior on the elevated plus maze were normal in transgenic subjects. Two robust phenotypic traits were observed. (i) Transge...

  4. Rheumatic manifestations of inflammatory bowel disease

    Rodríguez-Reyna, Tatiana Sofía; Martínez-Reyes, Cynthia; Yamamoto-Furusho, Jesús Kazúo

    2009-01-01

    This article reviews the literature concerning rheumatic manifestations of inflammatory bowel disease (IBD), including common immune-mediated pathways, frequency, clinical course and therapy. Musculoskeletal complications are frequent and well-recognized manifestations in IBD, and affect up to 33% of patients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations, notably in HLA-B27 transgenic rats. The autoimmune...

  5. Age-related autocrine diabetogenic effects of transgenic resistin in spontaneously hypertensive rats: gene expression profile analysis

    Pravenec, Michal; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Šilhavý, J.; Maxová, M.; Kazdová, L.; Seidman, J. G.; Seidman, Ch. E.; Eminaga, S.; Gorham, J.; Wang, J.; Kurtz, T. W.

    2011-01-01

    Roč. 43, č. 7 (2011), s. 372-379. ISSN 1094-8341 R&D Projects: GA MŠk(CZ) ME08006; GA MŠk(CZ) 1M0510; GA AV ČR(CZ) IAA500110805; GA MZd(CZ) NS9759 Grant ostatní: Fondation Leducq(FR) 06CVD03 Institutional research plan: CEZ:AV0Z50110509 Keywords : transgenic rat * adipose tissue * insulin resistance * autocrine effects Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.735, year: 2011

  6. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein.

    Malínská, Hana; Oliyarnyk, Olena; Škop, Vojtěch; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, Ludmila; Pravenec, Michal

    2016-01-01

    Inflammation and oxidative and dicarbonyl stress play important roles in the pathogenesis of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver. However, its "pleiotropic" effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, using spontaneously hypertensive rats that transgenically express human C-reactive protein (SHR-CRP). We treated 8-month-old male transgenic SHR-CRP rats with metformin (5 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP rats were fed a standard diet without metformin. In a similar fashion, we studied a group of nontransgenic SHR treated with metformin and an untreated group of nontransgenic SHR controls. In each group, we studied 6 animals. Parameters of glucose and lipid metabolism and oxidative and dicarbonyl stress were measured using standard methods. Gene expression profiles were determined using Affymetrix GeneChip Arrays. Statistical significance was evaluated by two-way ANOVA. In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFα and MCP-1 while levels of human CRP remained unchanged. Metformin significantly reduced oxidative stress (levels of conjugated dienes and TBARS) and dicarbonyl stress (levels of methylglyoxal) in left ventricles, but not in kidneys. No significant effects of metformin on oxidative and dicarbonyl stress were observed in SHR controls. In addition, metformin treatment reduced adipose tissue lipolysis associated with human CRP. Possible molecular mechanisms of metformin action-studied by gene expression profiling in the liver-revealed deregulated genes from inflammatory and insulin signaling, AMP

  7. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

    Malínská, Hana; Oliyarnyk, Olena; Škop, Vojtěch; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, Ludmila; Pravenec, Michal

    2016-01-01

    Inflammation and oxidative and dicarbonyl stress play important roles in the pathogenesis of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver. However, its “pleiotropic” effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, using spontaneously hypertensive rats that transgenically express human C-reactive protein (SHR-CRP). We treated 8-month-old male transgenic SHR-CRP rats with metformin (5 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP rats were fed a standard diet without metformin. In a similar fashion, we studied a group of nontransgenic SHR treated with metformin and an untreated group of nontransgenic SHR controls. In each group, we studied 6 animals. Parameters of glucose and lipid metabolism and oxidative and dicarbonyl stress were measured using standard methods. Gene expression profiles were determined using Affymetrix GeneChip Arrays. Statistical significance was evaluated by two-way ANOVA. In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFα and MCP-1 while levels of human CRP remained unchanged. Metformin significantly reduced oxidative stress (levels of conjugated dienes and TBARS) and dicarbonyl stress (levels of methylglyoxal) in left ventricles, but not in kidneys. No significant effects of metformin on oxidative and dicarbonyl stress were observed in SHR controls. In addition, metformin treatment reduced adipose tissue lipolysis associated with human CRP. Possible molecular mechanisms of metformin action–studied by gene expression profiling in the liver–revealed deregulated genes from inflammatory and insulin signaling, AMP

  8. A progressive dopaminergic phenotype associated with neurotoxic conversion of α-synuclein in BAC-transgenic rats.

    Nuber, Silke; Harmuth, Florian; Kohl, Zacharias; Adame, Anthony; Trejo, Margaritha; Schönig, Kai; Zimmermann, Frank; Bauer, Claudia; Casadei, Nicolas; Giel, Christiane; Calaminus, Carsten; Pichler, Bernd J; Jensen, Poul H; Müller, Christian P; Amato, Davide; Kornhuber, Johannes; Teismann, Peter; Yamakado, Hodaka; Takahashi, Ryosuke; Winkler, Juergen; Masliah, Eliezer; Riess, Olaf

    2013-02-01

    Conversion of soluble α-synuclein into insoluble and fibrillar inclusions is a hallmark of Parkinson's disease and other synucleinopathies. Accumulating evidence points towards a relationship between its generation at nerve terminals and structural synaptic pathology. Little is known about the pathogenic impact of α-synuclein conversion and deposition at nigrostriatal dopaminergic synapses in transgenic mice, mainly owing to expression limitations of the α-synuclein construct. Here, we explore whether both the rat as a model and expression of the bacterial artificial chromosome construct consisting of human full-length wild-type α-synuclein could exert dopaminergic neuropathological effects. We found that the human promoter induced a pan-neuronal expression, matching the rodent α-synuclein expression pattern, however, with prominent C-terminally truncated fragments. Ageing promoted conversion of both full-length and C-terminally truncated α-synuclein species into insolube and proteinase K-resistant fibres, with strongest accumulation in the striatum, resembling biochemical changes seen in human Parkinson's disease. Transgenic rats develop early changes in novelty-seeking, avoidance and smell before the progressive motor deficit. Importantly, the observed pathological changes were associated with severe loss of the dopaminergic integrity, thus resembling more closely the human pathology. PMID:23413261

  9. Nicotine mediates expression of genes related to antioxidant capacity and oxidative stress response in HIV-1 transgenic rat brain.

    Song, Guohua; Nesil, Tanseli; Cao, Junran; Yang, Zhongli; Chang, Sulie L; Li, Ming D

    2016-02-01

    Oxidative stress plays an important role in the progression of HIV-1 infection. Nicotine can either protect neurons from neurodegeneration or induce oxidative stress, depending on its dose and degree of oxidative stress impairment. However, the relationship between nicotine and oxidative stress in the HIV-1-infected individuals remains largely unknown. The purpose of this study was to determine the effect of nicotine on expression of genes related to the glutathione (GSH)-centered antioxidant system and oxidative stress in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of HIV-1 transgenic (HIV-1Tg) and F344 control rats. Adult HIV-1Tg and F344 rats received nicotine (0.4 mg/kg, base, s.c.) or saline injections once per day for 27 days. At the end of treatment, various brain regions including the NAc and VTA were collected from each rat. Following total RNA extraction and complementary DNA (cDNA) synthesis of each sample, quantitative reverse transcription PCR (RT-PCR) analysis was performed for 43 oxidative-stress-related genes. Compared with F344 control rats, HIV-1Tg rats showed a significant downregulation of genes involved in ATPase and cyctochrome oxidase at the messenger RNA (mRNA) level in both regions. Further, we found a significant downregulation of Gstm5 in the NAc and upregulation of Cox1, Cox3, and Gsta6 in the VTA of HIV-1Tg rats. HIV-1Tg rats showed brain-region-specific responses to chronic nicotine treatment. This response resulted in a change in the expression of genes involved in antioxidant mechanisms including the downregulation of genes such as Atp5h, Calml1, Gpx7, Gstm5, Gsr, and Gsta6 and upregulation of Sod1 in the NAc, as well as downregulation of genes like Cox5a, Gpx4, Gpx6, Gpx7, Gstm5, and Sod1 in the VTA of HIV-1Tg rats. Together, we conclude that chronic nicotine treatment has a dual effect on the antioxidant defense system and oxidative-stress-induced apoptosis signaling in HIV-1Tg rats. These findings suggest that

  10. Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats.

    Guo, Qian-ying; He, Li-xia; Zhu, Han; Shang, Jun-li; Zhu, Ling-yan; Wang, Jun-bo; Li, Yong

    2015-12-01

    BT799 is a genetically modified (GM) maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt). The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58) at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control. PMID:26633453

  11. Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats

    Qian-ying Guo

    2015-12-01

    Full Text Available BT799 is a genetically modified (GM maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt. The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58 at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control.

  12. A Vitamin A Deficient Diet Enhances Proinflammatory Cytokine, Mu Opioid Receptor, and HIV-1 Expression in the HIV-1 Transgenic Rat

    Royal, Walter; III,; Wang, Huiyun; Jones, Odell; Tran, Hieu; Bryant, Joseph L.

    2007-01-01

    The HIV-1 (HIV) transgenic (Tg) rat develops several immune abnormalities in association with clinical impairments that are similar to what are seen with HIV infection in humans. In HIV infection, retinoids and opioids can have separate and potentially combined effects on the clinical course of HIV disease. In these studies, the effects of a vitamin A deficient diet on T cell proinflammatory cytokine and mu opioid receptor (MOR) expression were examined in the Tg and in wild-type (WT) rats. T...

  13. Light-evoked somatosensory perception of transgenic rats that express channelrhodopsin-2 in dorsal root ganglion cells.

    Zhi-Gang Ji

    Full Text Available In vertebrate somatosensory systems, each mode of touch-pressure, temperature or pain is sensed by sensory endings of different dorsal root ganglion (DRG neurons, which conducted to the specific cortical loci as nerve impulses. Therefore, direct electrical stimulation of the peripheral nerve endings causes an erroneous sensation to be conducted by the nerve. We have recently generated several transgenic lines of rat in which channelrhodopsin-2 (ChR2 transgene is driven by the Thy-1.2 promoter. In one of them, W-TChR2V4, some neurons were endowed with photosensitivity by the introduction of the ChR2 gene, coding an algal photoreceptor molecule. The DRG neurons expressing ChR2 were immunohistochemically identified using specific antibodies to the markers of mechanoreceptive or nociceptive neurons. Their peripheral nerve endings in the plantar skin as well as the central endings in the spinal cord were also examined. We identified that ChR2 is expressed in a certain population of large neurons in the DRG of W-TChR2V4. On the basis of their morphology and molecular markers, these neurons were classified as mechanoreceptive but not nociceptive. ChR2 was also distributed in their peripheral sensory nerve endings, some of which were closely associated with CK20-positive cells to form Merkel cell-neurite complexes or with S-100-positive cells to form structures like Meissner's corpuscles. These nerve endings are thus suggested to be involved in the sensing of touch. Each W-TChR2V4 rat showed a sensory-evoked behavior in response to blue LED flashes on the plantar skin. It is thus suggested that each rat acquired an unusual sensory modality of sensing blue light through the skin as touch-pressure. This light-evoked somatosensory perception should facilitate study of how the complex tactile sense emerges in the brain.

  14. Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of gama-lacI transgenic rats.

    Topinka, Jan; Loli, P.; Hurbánková, M.; Kováčiková, Z.; Volkovová, K.; Wolff, T.; Oesterle, D.; Kyrtopoulos, S.A.; Georgiadis, P.

    2006-01-01

    Roč. 595, - (2006), s. 167-173. ISSN 0027-5107 Institutional research plan: CEZ:AV0Z50390512 Keywords : transgenic rats * mineral fibres * mutations Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 4.111, year: 2006

  15. Sterol regulatory element binding protein 2 overexpression is associated with reduced adipogenesis and ectopic fat accumulation in transgenic spontaneously hypertensive rats

    Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Trnovská, J.; Kazdová, L.; Pravenec, Michal

    2014-01-01

    Roč. 63, č. 5 (2014), s. 587-590. ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH12061 Institutional support: RVO:67985823 Keywords : sterol regulatory element binding protein 2 * transgenic * spontaneously hypertensive rat * lipid metabolism Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.293, year: 2014

  16. Transgenic Animal Mutation Assays

    Tao Chen; Ph.D.D.A.B.T.

    2005-01-01

    @@ The novel transgenic mouse and rat mutation assays have provided a tool for analyzing in vivo mutation in any tissue, thus permitting the direct comparison of cancer incidence with mutant frequency.

  17. Combined renin inhibition/(prorenin receptor blockade in diabetic retinopathy--a study in transgenic (mREN227 rats.

    Wendy W Batenburg

    Full Text Available Dysfunction of renin-angiotensin system (RAS contributes to the pathogenesis of diabetic retinopathy (DR. Prorenin, the precursor of renin is highly elevated in ocular fluid of diabetic patients with proliferative retinopathy. Prorenin may exert local effects in the eye by binding to the so-called (prorenin receptor ((PRR. Here we investigated the combined effects of the renin inhibitor aliskiren and the putative (PRR blocker handle-region peptide (HRP on diabetic retinopathy in streptozotocin (STZ-induced diabetic transgenic (mRen227 rats (a model with high plasma prorenin levels as well as prorenin stimulated cytokine expression in cultured Müller cells. Adult (mRen227 rats were randomly divided into the following groups: (1 non-diabetic; (2 diabetic treated with vehicle; (3 diabetic treated with aliskiren (10 mg/kg per day; and (4 diabetic treated with aliskiren+HRP (1 mg/kg per day. Age-matched non-diabetic wildtype Sprague-Dawley rats were used as control. Drugs were administered by osmotic minipumps for three weeks. Transgenic (mRen227 rat retinas showed increased apoptotic cell death of both inner retinal neurons and photoreceptors, increased loss of capillaries, as well as increased expression of inflammatory cytokines. These pathological changes were further exacerbated by diabetes. Aliskiren treatment of diabetic (mRen227 rats prevented retinal gliosis, and reduced retinal apoptotic cell death, acellular capillaries and the expression of inflammatory cytokines. HRP on top of aliskiren did not provide additional protection. In cultured Müller cells, prorenin significantly increased the expression levels of IL-1α and TNF-α, and this was completely blocked by aliskiren or HRP, their combination, (PRR siRNA and the AT1R blocker losartan, suggesting that these effects entirely depended on Ang II generation by (PRR-bound prorenin. In conclusion, the lack of effect of HRP on top of aliskiren, and the Ang II-dependency of the ocular

  18. A new transgenic rat model of hepatic steatosis and the metabolic syndrome

    Qi, N.R.; Wang, J.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Kazdová, L.; Pravenec, Michal; Kurtz, T. W.

    2005-01-01

    Roč. 45, č. 5 (2005), s. 1004-1011. ISSN 0194-911X R&D Projects: GA MZd(CZ) NB7403; GA MŠk(CZ) 1M0520 Grant ostatní: NIH(US) HL35018; NIH(US) HL63709; NIH(US) TW01236 Institutional research plan: CEZ:AV0Z50110509 Keywords : hepatic steatosis * Srebp1a * transgenic SHR Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.331, year: 2005

  19. Gene therapy for rat renal anemia with implantation of erythropoietin-transgenic myoblasts

    刘永学; 魏汉东; 吴祖泽; 贺福初

    1999-01-01

    To investigate whether an erythropoietin (EPO) gene-based therapy could serve as an alternative to the repeated injection of rhEPO in treatment to renal anemia, the genetically modified myoblasts of rats, named Myo/ EPO, were implanted through intramuscular injection to model rats with renal anemia. The hemoglobin (Hb) and hematocrit (HCT) of the rats increased from (92. 5±3.0) g/L and 0.29 ±0.04 to the peak values of (103.8 ±5.0) g/L and 0. 32 ±0. 04 respectively 14 d after implantation, and sustained the pre-implantation level for 90 d. Otherwise, the control rats implanted with Myo/X, which carried the parent retroviral vector, gradually became severe in anemia. The PCR detection for hEPO cDNA in the rat muscle adjacent to injection sites indicated that the Myo/EPO cells survived for a long period in the muscle of rats. The results primarily demonstrate that myoblast gene transfer of EPO is effective for the treatment of rat renal anemia.

  20. Primary T-cells from human CD4/CCR5-transgenic rats support all early steps of HIV-1 replication including integration, but display impaired viral gene expression

    Hermann Volker

    2007-07-01

    Full Text Available Abstract Background In vivo studies on HIV-1 pathogenesis and testing of antiviral strategies have been hampered by the lack of an immunocompetent small animal model that is highly susceptible to HIV-1 infection. Since native rodents are non-permissive, we developed transgenic rats that selectively express the HIV-1 receptor complex, hCD4 and hCCR5, on relevant target cells. These animals display a transient low-level plasma viremia after HIV-1YU-2 infection, demonstrating HIV-1 susceptibility in vivo. However, unlike macrophages, primary CD4 T-cells from double-transgenic animals fail to support viral spread ex vivo. To identify quantitative limitations or absolute blocks in this rodent species, we quantitatively assessed the efficiency of key steps in the early phase of the viral replication cycle in a side-by-side comparison in infected cell lines and primary T-cells from hCD4/hCCR5-transgenic rats and human donors. Results Levels of virus entry, HIV-1 cDNA synthesis, nuclear import, and integration into the host genome were shown to be remarkably similar in cell lines and, where technically accessible, in primary T-cells from both species. In contrast, a profound impairment at the level of early HIV gene expression was disclosed at the single-cell level in primary rat T-cells and most other rat-derived cells. Macrophages were a notable exception, possibly reflecting the unique transcriptional milieu in this evolutionarily conserved target cell of all lentiviruses. Importantly, transient trans-complementation by ex vivo nucleofection with the Tat-interacting protein Cyclin T1 of human origin markedly elevated HIV gene expression in primary rat T-cells. Conclusion This is the first study that has quantitatively determined the efficiency of consecutive steps in the HIV-1 replication cycle in infected primary HIV target cells from a candidate transgenic small animal and compared it to human cells. Unlike cells derived from mice or rabbits, rat

  1. Benzo[a]pyrene-enhanced mutagenesis by asbestos in the lung of lambda-lacI transgenic rats.

    Loli, P; Topinka, J; Georgiadis, P; Dusinská, M; Hurbánková, M; Kováciková, Z; Volkovová, K; Wolff, T; Oesterle, D; Kyrtopoulos, S A

    2004-09-01

    To study the suspected mechanism of the interaction between tobacco smoking and asbestos exposure in the modulation of cancer risk, the mutagenic potential of asbestos in combination with the tobacco smoke carcinogen benzo[a]pyrene (B[a]P) was examined in vivo in the rat lung. B[a]P was administered intratracheally in one set of experiments, or by two daily intraperitoneal injections in another set of experiments, to lambdalacI transgenic rats, together with 1, 2 or 4 x 2 mg amosite in one experiment. In the first experiment, the combined action of amosite and B[a]P caused a synergistic (superadditive) increase of mutation frequency in the lung, as compared to groups treated only with asbestos or B[a]P. In the second experiment, i.p. treatment with B[a]P did not significantly alter the mutation frequency induced by amosite, neither after 4 nor after 16 weeks of exposure. The B[a]P-DNA adduct levels were unaffected by amosite co-treatment in both experiments. We assume that the synergistic increase of mutation frequency after intratracheal treatment was due to the mitogenic activities of B[a]P and of amosite. In conclusion, our findings indicate that a weak and delayed mutagenic effect of amosite in rat lung observed in another study was strongly enhanced by the concomitant action of B[a]P. The striking enhancement effect of B[a]P may provide a basis for understanding the suspected synergism of smoking on asbestos carcinogenesis. PMID:15288535

  2. Characterization of microglia/macrophages in gliomas developed in S-100β-v-erbB transgenic rats.

    Sasaki, Atsushi; Yokoo, Hideaki; Tanaka, Yuko; Homma, Taku; Nakazato, Yoichi; Ohgaki, Hiroko

    2013-10-01

    Glioma-infiltrating microglia/macrophages are referred to as tumor-associated macrophages (TAMs). Transgenic (TG) rats expressing v-erbB, which is a viral form of the epidermal growth factor receptor, under transcriptional regulation by the S100-β promoter, develop brain tumors. This study was designed to clarify the pathological characteristics of TAMs in these experimental tumors. We carried out immunohistochemical and morphometrical analyses of microglia/macrophages in brain tumors (5 malignant glioma, 4 anaplastic oligodendroglioma, 4 astrocytoma) that developed in TG rats. TAMs with ionized calcium-binding adaptor molecule 1 (Iba1) positivity and morphology of activated, non-phagocytic microglia increased within and around the tumors in malignant gliomas and anaplastic astrocytomas. The Iba1-positive TAMs of the tumor core were significantly more activated than Iba1-positive microglia of non-neoplastic brain tissue in intraparenchymal anaplastic oligodendrogliomas. Iba1 expression showed a significant positive correlation to Ki-67 expression in all the gliomas. Most TAMs showed no or little expression against CD68, CD163 or CD204, although CD204-positive TAMs were observed in necrosis as well as in the proliferating vascular wall. In conclusion, S-100β-v-erbB TG rats may serve as a useful animal model for further analysis of TAMs in terms of tumor cell proliferation, microvascular proliferation and phagocytosis, and as a tool for therapeutic use in malignant gliomas, although it should be noted that the polarization of TAMs toward the M2 phenotype remains unclear. PMID:23331472

  3. Demonstration of the functional impact of vasopressin signaling in the thick ascending limb by a targeted transgenic rat approach.

    Mutig, Kerim; Borowski, Tordis; Boldt, Christin; Borschewski, Aljona; Paliege, Alexander; Popova, Elena; Bader, Michael; Bachmann, Sebastian

    2016-08-01

    The antidiuretic hormone vasopressin (AVP) regulates renal salt and water reabsorption along the distal nephron and collecting duct system. These effects are mediated by vasopressin 2 receptors (V2R) and release of intracellular Gs-mediated cAMP to activate epithelial transport proteins. Inactivating mutations in the V2R gene lead to the X-linked form of nephrogenic diabetes insipidus (NDI), which has chiefly been related with impaired aquaporin 2-mediated water reabsorption in the collecting ducts. Previous work also suggested the AVP-V2R-mediated activation of Na(+)-K(+)-2Cl(-)-cotransporters (NKCC2) along the thick ascending limb (TAL) in the context of urine concentration, but its individual contribution to NDI or, more generally, to overall renal function was unclear. We hypothesized that V2R-mediated effects in TAL essentially determine its reabsorptive function. To test this, we reevaluated V2R expression. Basolateral membranes of medullary and cortical TAL were clearly stained, whereas cells of the macula densa were unreactive. A dominant-negative, NDI-causing truncated V2R mutant (Ni3-Glu242stop) was then introduced into the rat genome under control of the Tamm-Horsfall protein promoter to cause a tissue-specific AVP-signaling defect exclusively in TAL. Resulting Ni3-V2R transgenic rats revealed decreased basolateral but increased intracellular V2R signal in TAL epithelia, suggesting impaired trafficking of the receptor. Rats displayed significant baseline polyuria, failure to concentrate the urine in response to water deprivation, and hypercalciuria. NKCC2 abundance, phosphorylation, and surface expression were markedly decreased. In summary, these data indicate that suppression of AVP-V2R signaling in TAL causes major impairment in renal fluid and electrolyte handling. Our results may have clinical implications. PMID:27306979

  4. A robust method for assessing chemically induced mutagenic effects in the oral cavity of transgenic Big Blue® rats.

    Young, Robert R; Thompson, Chad M; Dinesdurage, Harshini R; Elbekai, Reem H; Suh, Mina; Rohr, Annette C; Proctor, Deborah M

    2015-08-01

    The Big Blue® (BB) in vivo mutation assay uses transgenic rodents to measure treatment-induced mutations in virtually any tissue. The BB assay can be conducted in rats or mice and is ideal for investigating tissue-specific mutagenic mode of action of tumor induction. Some tissues such as oral mucosa have not been thoroughly studied. Due to the small quantity and cartilaginous nature of oral cavity tissues, development of special prosection and DNA isolation methods was required to permit robust analysis of mutations in these tissues. Improved surgical methods permitted collection of adequate and reproducible quantities of tissue (∼45 mg gingiva/buccal and ∼30 mg gingiva/palate). Optimized DNA isolation methods included use of liquid nitrogen pulverization, homogenization, nuclei pelleting, digestion, and phenol/chloroform extraction, to yield sufficient quantities of DNA from these tissues. In preliminary optimization work, mutant frequency (MF) in tongue and gingiva was increased in rats exposed to the promutagen, benzo[a]pyrene, and the direct mutagen, N-ethyl-N-nitrosourea. The oral cavity carcinogen, 4-nitroquinoline-1-oxide (4-NQO; 10 ppm in drinking water; 28 days), was qualified as a positive control for mutagenesis in oral tissues since it caused significant increases in cII MFs in gingiva/palate (50.2-fold) and gingiva/buccal tissues (21.3-fold), but not in liver or bone marrow (0.9- and 1.4-fold, respectively). These results are consistent with the observation that 4-NQO primarily induces tumors in oral cavity. Results also demonstrate the utility of the BB rat mutation assay and optimized methods for investigation of oral cavity mutagenicity, and by extension, analysis of other small and cartilaginous tissues. PMID:25969955

  5. Dietary effects of soy isoflavones daidzein and genistein on 7,12-dimethylbenz[a]anthracene-induced mammary mutagenesis and carcinogenesis in ovariectomized Big Blue transgenic rats.

    Manjanatha, Mugimane; Shelton, Sharon; Bishop, Michelle; Lyn-Cook, Lascelles; Aidoo, Anane

    2006-01-01

    Dietary modulation of cancer & cancer biomarkers. Dietary item or component studied: the isoflavones daidzein (DZ) and genistein (GE)Outcome studied: Mammary gland hyperplasia; DNA damage. Study type: Big Blue transgenic rats Tissue/biological material/sample size: mammary glands; lymphocytes isolated from the spleen. Mode of exposure: dietary. Impact on outcome (including dose-response): The isoflavones or E(2) supplementation alone resulted in the lac I MFs that were not significantly diff...

  6. Fumaric Acid Esters Can Block Pro-Inflammatory Actions of Human CRP and Ameliorate Metabolic Disturbances in Transgenic Spontaneously Hypertensive Rats

    Šilhavý, Jan; Zídek, Václav; Mlejnek, Petr; Landa, Vladimír; Šimáková, Miroslava; Strnad, Hynek; Oliyarnyk, O.; Škop, V.; Kazdová, L.; Kurtz, T.; Pravenec, Michal

    2014-01-01

    Roč. 9, č. 7 (2014), e101906. E-ISSN 1932-6203 R&D Projects: GA MZd(CZ) NT14325; GA MŠk(CZ) LH12061; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : fumaric acid esters * C-reactive protein * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  7. A transgenic rat expressing human APP with the Swedish Alzheimer's disease mutation

    Folkesson, Ronnie; Malkiewicz, Katarzyna; Kloskowska, Ewa;

    2007-01-01

    protein (APP) containing the Swedish AD mutation. The highest level of expression in the brain is found in the cortex, hippocampus, and cerebellum. Starting after the age of 15 months, the rats show increased tau phosphorylation and extracellular Abeta staining. The Abeta is found predominantly in...

  8. HIV-1 Transgenic Rats Display Alterations in Immunophenotype and Cellular Responses Associated with Aging

    Abbondanzo, Susan J.; Chang, Sulie L.

    2014-01-01

    Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in immune response changes, alterations in immunological phenotypes, and ultimately increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV-1 disease, parti...

  9. Transgenic rescue of defective Cd36 enhances myocardial adenylyl cyclase signaling in spontaneously hypertensive rats

    Klevstig, M.; Manakov, D.; Kašparová, D.; Brabcová, I.; Papoušek, František; Žurmanová, J.; Zídek, Václav; Šilhavý, Jan; Neckář, Jan; Pravenec, Michal; Kolář, František; Nováková, O.; Novotný, J.

    2013-01-01

    Roč. 465, č. 10 (2013), s. 1477-1486. ISSN 0031-6768 R&D Projects: GA MŠk(CZ) LL1204; GA AV ČR(CZ) IAAX01110901; GA ČR(CZ) GAP303/10/0505 Institutional support: RVO:67985823 Keywords : SHR rats * Cd36 * heart * beta-Adrenergic receptors * Adenylyl cyclase * Protein kinase A Subject RIV: ED - Physiology Impact factor: 3.073, year: 2013

  10. Characterization of sevoflurane effects on Per2 expression using ex vivo bioluminescence imaging of the suprachiasmatic nucleus in transgenic rats.

    Matsuo, Izumi; Iijima, Norio; Takumi, Ken; Higo, Shimpei; Aikawa, Satoko; Anzai, Megumi; Ishii, Hirotaka; Sakamoto, Atsuhiro; Ozawa, Hitoshi

    2016-06-01

    The inhalation anesthetic sevoflurane suppresses Per2 expression in the suprachiasmatic nucleus (SCN) in rodents. Here, we investigated the intra-SCN regional specificity, time-dependency, and pharmacological basis of sevoflurane-effects. Bioluminescence image was taken from the SCN explants of mPer2 promoter-destabilized luciferase transgenic rats, and each small regions of interest (ROI) of the image was analyzed. Sevoflurane suppressed bioluminescence in all ROIs, suggesting that all regions in the SCN are sensitive to sevoflurane. Clear time-dependency in sevoflurane effects were also observed; application during the trough phase of the bioluminescence cycle suppressed the subsequent increase in bioluminescence and resulted in a phase delay of the cycle; sevoflurane applied during the middle of the ascending phase induced a phase advance; sevoflurane on the descending phase showed no effect. These results indicate that the sevoflurane effect may depend on the intrinsic state of circadian machinery. Finally, we examined the involvement of GABAergic signal transduction in the sevoflurane effect. Co-application of both GABAA and GABAB receptor antagonists completely blocked the effect of sevoflurane on the bioluminescence rhythm, suggesting that sevoflurane inhibits Per2 expression via GABAergic signal transduction. Current study elucidated the anesthetic effects on the molecular mechanisms of circadian rhythm. PMID:26696094

  11. Transgenic Rat Model of Huntington’s Disease: A Histopathological Study and Correlations with Neurodegenerative Process in the Brain of HD Patients

    Yvona Mazurová

    2014-01-01

    Full Text Available Rats transgenic for Huntington’s disease (tgHD51 CAG rats, surviving up to two years, represent an animal model of HD similar to the late-onset form of human disease. This enables us to follow histopathological changes in course of neurodegenerative process (NDP within the striatum and compare them with postmortem samples of human HD brains. A basic difference between HD pathology in human and tgHD51 rats is in the rate of NDP progression that originates primarily from slow neuronal degeneration consequently resulting in lesser extent of concomitant reactive gliosis in the brain of tgHD51 rats. Although larger amount of striatal neurons displays only gradual decrease in their size, their number is significantly reduced in the oldest tgHD51 rats. Our quantitative analysis proved that the end of the first year represents the turn in the development of morphological changes related to the progression of NDP in tgHD51 rats. Our data also support the view that all types of CNS glial cells play an important, irreplaceable role in NDP. To the best of our knowledge, our findings are the first to document that tgHD51 CAG rats can be used as a valid animal model for detailed histopathological studies related to HD in human.

  12. Plasmid-based genetic modification of human bone marrow-derived stromal cells: analysis of cell survival and transgene expression after transplantation in rat spinal cord

    Van Tendeloo Viggo FI

    2007-12-01

    Full Text Available Abstract Background Bone marrow-derived stromal cells (MSC are attractive targets for ex vivo cell and gene therapy. In this context, we investigated the feasibility of a plasmid-based strategy for genetic modification of human (hMSC with enhanced green fluorescent protein (EGFP and neurotrophin (NT3. Three genetically modified hMSC lines (EGFP, NT3, NT3-EGFP were established and used to study cell survival and transgene expression following transplantation in rat spinal cord. Results First, we demonstrate long-term survival of transplanted hMSC-EGFP cells in rat spinal cord under, but not without, appropriate immune suppression. Next, we examined the stability of EGFP or NT3 transgene expression following transplantation of hMSC-EGFP, hMSC-NT3 and hMSC-NT3-EGFP in rat spinal cord. While in vivo EGFP mRNA and protein expression by transplanted hMSC-EGFP cells was readily detectable at different time points post-transplantation, in vivo NT3 mRNA expression by hMSC-NT3 cells and in vivo EGFP protein expression by hMSC-NT3-EGFP cells was, respectively, undetectable or declined rapidly between day 1 and 7 post-transplantation. Further investigation revealed that the observed in vivo decline of EGFP protein expression by hMSC-NT3-EGFP cells: (i was associated with a decrease in transgenic NT3-EGFP mRNA expression as suggested following laser capture micro-dissection analysis of hMSC-NT3-EGFP cell transplants at day 1 and day 7 post-transplantation, (ii did not occur when hMSC-NT3-EGFP cells were transplanted subcutaneously, and (iii was reversed upon re-establishment of hMSC-NT3-EGFP cell cultures at 2 weeks post-transplantation. Finally, because we observed a slowly progressing tumour growth following transplantation of all our hMSC cell transplants, we here demonstrate that omitting immune suppressive therapy is sufficient to prevent further tumour growth and to eradicate malignant xenogeneic cell transplants. Conclusion In this study, we

  13. The reduction of volume and fiber bundle connections in the hippocampus of EGR3 transgenic schizophrenia rats

    Ma E

    2015-07-01

    diffusion tensor and fiber bundles tracking. The fibronectin in relevant brain regions was also analyzed.Results: There was a significant decrease in the volume of the fiber beam through the left hippocampus dentate in the schizophrenia model group in comparison to the control group and the risperidone treatment group (P<0.05. A significant reduction in the volume and number of the fiber bundles was also observed in left prefrontal–left hippocampus, left hippocampus–left thalamus, left prefrontal–left hippocampus–left thalamus areas in the model group (all P<0.05.Conclusion: The volume of hippocampus and the number of fiber bundles were reduced in EGR3 transgenic schizophrenia rats, and are the most sensitive indicators in schizophrenia. The diffusion tensor imaging technique plays an important role in the evaluation of patients with schizophrenia. Keywords: magnetic resonance imaging, schizophrenia, early growth response factor 3, fractional anisotropy, diffusion tensor imaging 

  14. Functional magnetic resonance imaging in awake transgenic fragile X rats: evidence of dysregulation in reward processing in the mesolimbic/habenular neural circuit.

    Kenkel, W M; Yee, J R; Moore, K; Madularu, D; Kulkarni, P; Gamber, K; Nedelman, M; Ferris, C F

    2016-01-01

    Anxiety and social deficits, often involving communication impairment, are fundamental clinical features of fragile X syndrome. There is growing evidence that dysregulation in reward processing is a contributing factor to the social deficits observed in many psychiatric disorders. Hence, we hypothesized that transgenic fragile X mental retardation 1 gene (fmr1) KO (FX) rats would display alterations in reward processing. To this end, awake control and FX rats were imaged for changes in blood oxygen level dependent (BOLD) signal intensity in response to the odor of almond, a stimulus to elicit the innate reward response. Subjects were 'odor naive' to this evolutionarily conserved stimulus. The resulting changes in brain activity were registered to a three-dimensional segmented, annotated rat atlas delineating 171 brain regions. Both wild-type (WT) and FX rats showed robust brain activation to a rewarding almond odor, though FX rats showed an altered temporal pattern and tended to have a higher number of voxels with negative BOLD signal change from baseline. This pattern of greater negative BOLD was especially apparent in the Papez circuit, critical to emotional processing and the mesolimbic/habenular reward circuit. WT rats showed greater positive BOLD response in the supramammillary area, whereas FX rats showed greater positive BOLD response in the dorsal lateral striatum, and greater negative BOLD response in the retrosplenial cortices, the core of the accumbens and the lateral preoptic area. When tested in a freely behaving odor-investigation paradigm, FX rats failed to show the preference for almond odor which typifies WT rats. However, FX rats showed investigation profiles similar to WT when presented with social odors. These data speak to an altered processing of this highly salient novel odor in the FX phenotype and lend further support to the notion that altered reward systems in the brain may contribute to fragile X syndrome symptomology. PMID:27003189

  15. Study on correlation between ankylosing spondylitis and HLA -B27 subgenotype%强直性脊柱炎与 HLA-B27基因亚型的相关性研究

    王华; 甄拴平; 党丽君; 张树琪

    2016-01-01

    目的:探讨不同人类白细胞抗原B27(HLA‐B27)基因亚型与强直性脊柱炎(AS)的相关性。方法采集骨科、针灸风湿科门诊及住院患者静脉全血,应用基因分析法定性检测HLA‐B27,其中HLA‐B27阳性的AS确诊患者380例,并选取HLA‐B27阳性健康对照组50例,同时通过序列特异性引物PCR(PCR‐SSP)技术检测AS患者和健康对照组的 HLA‐B27基因亚型。结果380例A S患者中,检出 HLA‐B2704亚型217例(57.1%),HLA‐B2705亚型143例(37.6%),HLA‐B2707亚型11例(2.9%),HLA‐B2711亚型9例(2.4%);50例 HLA‐B27阳性健康对照组中,检出 HLA‐B2706亚型23例(46.0%),HLA‐B2709亚型21例(42.0%),HLA‐B2704亚型4例(8.0%),HLA‐B2705亚型2例(4.0%),两组比较差异有统计学意义( P=0.002)。结论宝鸡地区AS患者HLA‐B27基因亚型以B2704和B2705为主,与宝鸡地区汉族人群AS的发病呈强相关;B2706及B2709为该地区保护亚型。%Objective To explore the correlation between different HLA‐B27 subgenotype and ankylosing spondylitis (AS ) . Methods The whole venous blood was collected from the outpatients and inpatients of the orthopedics ,acupuncture and rheuma‐tism departments and HLA‐B27 was qualitatively detected by using the gene analysis method .Among them ,380 cases of AS were HLA‐B27 positive ,and 50 cases of HLA‐B27 positive were selected as the healthy control group .Then the HLA‐B27 subgenotypes were detected by using the sequence specific primers PCR (PCR‐SSP) technology .Results Among 380 cases of AS ,217 cases (57 .1% ) of HLA‐AS B2704 subgenotype ,143 cases (37 .6% ) of HLA‐B2705 subgenotype ,11 cases (2 .9% ) of HLA‐B2707 sub‐genotype and 9 cases (2 .4% ) of HLA‐B2711 subgenotype were detected out ;among 50 cases of HLA‐B27 positive in the healthy control group ,23 cases (46 .0% ) of HLA‐B2706 subgenotype ,21 cases (42 .0% ) of HLA‐B2709 subgenotype ,4 cases (8 .0% ) of HLA B2704 subgenotype and 2 cases (4 .0% ) of HLA‐B2705 subgenotype were detected out ,the differences between the two groups were statistically significant (P=0 .002) .Conclusion The subgenotypes of HLA‐B27 among the AS patients in Baoji area are dominated by the genotype B2704 and B2705 ,which is strongly correlated with the occurrence of AS among Han population in Baoji area ;B2706 and B2709 are the protective subgenotypes in this area .

  16. Ectopic bone formation and chondrodysplasia in transgenic mice carrying the rat C3(1)/T{sub AG} fusion gene

    Green, J.E.; Maroulakou, I.G.; Anver, M. [National Cancer Institute, Frederick, MD (United States)] [and others

    1994-09-01

    Transgenic mice expressing the SV40 large T-antigen (T{sup AG}) under the regultory control of the hormone-responsive rat C3(1) prostatein promoter develop unusual bone and cartilage lesions, as well as ectopic bone and cartilage formation. Two lines of transgenic animals have been propagated in which the expression of the transgene in chondrocytes results in a mild to moderate generalized disorganization of cartilage growth which appears to affect multiple tissues, including the trachea, ear pinna and articular cartilage. The epiphyseal plates are also affected with normal architecture of the zones of proliferation and maturation, but marked elongation of the zone of hypertrophy. Immunocytochemistry demonstrates that expression of T{sup AG} is limited to the zone of hypertropny in the epiphyseal plates, suggesting that the chondrocytes become hormone-responsive at this particular stage of differentiation. Normal mineralization and trabecular formation in long bone appears to occur. Ectopic bone and cartilage formation occurs in the foot pads of the fore- and hind- feet over the course of several months. This is preceded by proliferation of sweat gland epithelial cells followed by the appearance of nodules of cartilage and bone. The nodules are closely associated with proliferating epithelium but are not contiguous with bony structures normally found in the feet. The roles of BMP`s, growth factors, oncogenes and hormones in the development of these lesions will be presented. These transgenic animals may provide new insights into hormone-responsiveness of chondrocytes, as well as factors involved in the processes of bone and cartilage differentiation and growth. These transgenic animals may serve as a useful model for human heterotopic bone formation.

  17. Concerted In Vitro Trimming of Viral HLA-B27-Restricted Ligands by Human ERAP1 and ERAP2 Aminopeptidases

    Lorente, Elena; Barriga, Alejandro; Johnstone, Carolina; Mir, Carmen; Jiménez, Mercedes; López, Daniel

    2013-01-01

    In the classical human leukocyte antigen (HLA) class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases) and transported to the endoplasmic reticulum (ER) lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. ...

  18. HLA-B27致强直性脊柱炎的分子模拟学说

    吴俊玲; 郑山根

    2005-01-01

    1 HLA—B27的分子结构 HLA—B27与强直性脊柱炎(AS)是迄今所知的HLA与疾病相关性中最强和最典型的,其相对危险度达87.4%。B27是AS发病机制诸多学说中所共有的核心分子,研究B27分子对揭示其在AS中的作用是必须的。

  19. Transgenic mouse lines expressing rat AH receptor variants - A new animal model for research on AH receptor function and dioxin toxicity mechanisms

    Han/Wistar (Kuopio; H/W) rats are exceptionally resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity mainly because of their mutated aryl hydrocarbon receptor (AHR) gene. In H/W rats, altered splicing of the AHR mRNA generates two AHR proteins: deletion (DEL) and insertion (INS) variants, with the INS isoform being predominantly expressed. To gain further insight into their functional properties, cDNAs of these and rat wild-type (rWT) isoform were transferred into C57BL/6J-derived mice by microinjection. The endogenous mouse AHR was eliminated by selective crossing with Ahr-null mice. A single mouse line was obtained for each of the three constructs. The AHR mRNA levels in tissues were generally close to those of C57BL/6 mice in INS and DEL mice and somewhat higher in rWT mice; in testis, however, all 3 constructs exhibited marked overexpression. The transgenic mouse lines were phenotypically normal except for increased testis weight. Induction of drug-metabolizing enzymes by TCDD occurred similarly to that in C57BL/6 mice, but there tended to be a correlation with AHR concentrations, especially in testis. In contrast to C57BL/6 mice, the transgenics did not display any major gender difference in susceptibility to the acute lethality and hepatotoxicity of TCDD; rWT mice were highly sensitive, DEL mice moderately resistant and INS mice highly resistant. Co-expression of mouse AHR and rWT resulted in augmented sensitivity to TCDD and abolished the natural resistance of female C57BL/6 mice, whereas mice co-expressing mouse AHR and INS were resistant. Thus, these transgenic mouse lines provide a novel promising tool for molecular studies on dioxin toxicity and AHR function.

  20. Novel Transgenic Mouse Models Develop Retinal Changes Associated with Early Diabetic Retinopathy Similar to Those Observed in Rats with Diabetes Mellitus

    Guo, Changmei; Zhang, Zifeng; Zhang, Peng; Makita, Jun; Kawada, Hiroyoshi; Blessing, Karen; Kador, Peter F.

    2014-01-01

    Retinal capillary pericyte degeneration has been linked to aldose reductase (AR) activity in diabetic retinopathy (DR). Since the development of DR in mice and rats has been reported to differ and that this may be linked to differences in retinal sorbitol levels, we have established new murine models of early onset diabetes mellitus as tools for investigating the role of AR in DR. Transgenic diabetic mouse models were developed by crossbreeding diabetic C57BL/6-Ins2Akita/J (AK) with transgenic C57BL mice expressing green fluorescent protein (GFP), human aldose reductase (hAR) or both in vascular tissues containing smooth muscle actin-α (SMAA). Changes in retinal sorbitol levels were determined by HPLC while changes of growth factors and signaling were investigated by Western Blots. Retinal vascular changes were quantitatively analyzed on elastase-digestion flat mounts. Results show that sorbitol levels were higher in neural retinas of diabetic AK-SMAA-GFP-hAR compared to AK-SMAA-GFP mice. AK-SMAA-GFP-hAR mice showed induction of the retinal growth factors VEGF, IGF-1, bFGF and TGFβ, as well as signaling changes in P-Akt, P-SAPK/JNK, and P-44/42 MAPK. Increased loss of nuclei per capillary length and a significant increase in the percentage of acellular capillaries presented in 18 week old AK-SMAA-GFP-hAR mice. These changes are similar to those observed in streptozotocin-induced diabetic rats. Retinal changes in both mice and rats were prevented by inhibition of AR. These studies confirm that the increased expression of AR in mice results in the development of retinal changes associated with the early stages of DR that are similar to those observed in rats. PMID:24370601

  1. Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivo

    Littman Dan R

    2009-01-01

    Full Text Available Abstract Background Cells derived from native rodents have limits at distinct steps of HIV replication. Rat primary CD4 T-cells, but not macrophages, display a profound transcriptional deficit that is ameliorated by transient trans-complementation with the human Tat-interacting protein Cyclin T1 (hCycT1. Results Here, we generated transgenic rats that selectively express hCycT1 in CD4 T-cells and macrophages. hCycT1 expression in rat T-cells boosted early HIV gene expression to levels approaching those in infected primary human T-cells. hCycT1 expression was necessary, but not sufficient, to enhance HIV transcription in T-cells from individual transgenic animals, indicating that endogenous cellular factors are critical co-regulators of HIV gene expression in rats. T-cells from hCD4/hCCR5/hCycT1-transgenic rats did not support productive infection of prototypic wild-type R5 HIV-1 strains ex vivo, suggesting one or more significant limitation in the late phase of the replication cycle in this primary rodent cell type. Remarkably, we identify a replication-competent HIV-1 GFP reporter strain (R7/3 YU-2 Env that displays characteristics of a spreading, primarily cell-to-cell-mediated infection in primary T-cells from hCD4/hCCR5-transgenic rats. Moreover, the replication of this recombinant HIV-1 strain was significantly enhanced by hCycT1 transgenesis. The viral determinants of this so far unique replicative ability are currently unknown. Conclusion Thus, hCycT1 expression is beneficial to de novo HIV infection in a transgenic rat model, but additional genetic manipulations of the host or virus are required to achieve full permissivity.

  2. Effects of peripherally administered cholecystokinin-8 and secretin on feeding/drinking and oxytocin-mRFP1 fluorescence in transgenic rats.

    Motojima, Yasuhito; Kawasaki, Makoto; Matsuura, Takanori; Saito, Reiko; Yoshimura, Mitsuhiro; Hashimoto, Hirofumi; Ueno, Hiromichi; Maruyama, Takashi; Suzuki, Hitoshi; Ohnishi, Hideo; Sakai, Akinori; Ueta, Yoichi

    2016-08-01

    Peripheral administration of cholecystokinin (CCK)-8 or secretin activates oxytocin (OXT)-secreting neurons in the hypothalamus. Although OXT is involved in the regulation of feeding behavior, detailed mechanism remains unclear. In the present study, we examined the central OXTergic pathways after intraperitoneally (i.p.) administration of CCK-8 and secretin using male OXT-monomeric red fluorescent protein 1 (mRFP1) transgenic rats and male Wistar rats. I.p. administration of CCK-8 (50μg/kg) and secretin (100μg/kg) decreased food intake in these rats. While i.p. administration of CCK-8 decreased water intake, i.p. administration of secretin increased water intake. Immunohistochemical study revealed that Fos-Like-Immunoreactive cells were observed abundantly in the brainstem and in the OXT neurons in the dorsal division of the parvocellular paraventricular nucleus (dpPVN). We could observe marked increase of mRFP1 fluorescence, as an indicator for OXT, in the dpPVN and mRFP1-positive granules in axon terminals of the dpPVN OXT neurons in the nucleus tractus solitarius (NTS) after i.p. administration of CCK-8 and secretin. These results provide us the evidence that, at least in part, i.p. administration of CCK-8 or secretin might be involved in the regulation of feeding/drinking via a OXTergic pathway from the dpPVN to the NTS. PMID:26919961

  3. Transgen kunst

    2007-01-01

    Oversættelse af kunstneren Eduardo Kac' tekst "Transgenic Art" i Passepartout #27. Interfacekulturens æstetik. Udgivelsesdato: 28.04.07......Oversættelse af kunstneren Eduardo Kac' tekst "Transgenic Art" i Passepartout #27. Interfacekulturens æstetik. Udgivelsesdato: 28.04.07...

  4. Severely impaired hippocampal neurogenesis associates with an early serotonergic deficit in a BAC α-synuclein transgenic rat model of Parkinson's disease.

    Kohl, Zacharias; Ben Abdallah, Nada; Vogelgsang, Jonathan; Tischer, Lucas; Deusser, Janina; Amato, Davide; Anderson, Scott; Müller, Christian P; Riess, Olaf; Masliah, Eliezer; Nuber, Silke; Winkler, Jürgen

    2016-01-01

    Parkinson's disease (PD) is a multisystem disorder, involving several monoaminergic neurotransmitter systems resulting in a broad range of motor and non-motor symptoms. Pathological hallmarks of PD are the loss of dopaminergic neurons and the accumulation of alpha-synuclein, however also being present in the serotonergic raphe nuclei early in the disease course. The dysfunction of the serotonergic system projecting to the hippocampus may contribute to early non-motor symptoms such as anxiety and depression. The adult hippocampal dentate gyrus (DG), a unique niche of the forebrain continuously generating new neurons, may particularly present enhanced susceptibility towards accumulating alpha-synuclein levels. The underlying molecular mechanisms in the context of neuronal maturation and survival of new-born neurons are yet not well understood. To characterize the effects of overexpression of human full-length alpha-synuclein on hippocampal cellular and synaptic plasticity, we used a recently generated BAC alpha-synuclein transgenic rat model showing important features of PD such as widespread and progressive alpha-synuclein aggregation pathology, dopamine loss and age-dependent motor decline. At the age of four months, thus prior to the occurrence of the motor phenotype, we observed a profoundly impaired dendritogenesis of neuroblasts in the hippocampal DG resulting in severely reduced survival of adult new-born neurons. Diminished neurogenesis concurred with a serotonergic deficit in the hippocampus as defined by reduced levels of serotonin (5-HT) 1B receptor, decreased 5-HT neurotransmitter levels, and a loss of serotonergic nerve terminals innervating the DG/CA3 subfield, while the number of serotonergic neurons in the raphe nuclei remained unchanged. Moreover, alpha-synuclein overexpression reduced proteins involved in vesicle release, in particular synapsin-1 and Rab3 interacting molecule (RIM3), in conjunction with an altered ultrastructural architecture of

  5. Astrocytes and Müller cells changes during retinal degeneration in a transgenic rat model of retinitis pigmentosa.

    Laura eFernández-Sánchez

    2015-12-01

    Full Text Available Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer of P23H versus SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina.

  6. Anxiolytic- and antidepressant-like effects of angiotensin-(1-7) in hypertensive transgenic (mRen2)27 rats.

    Almeida-Santos, Ana Flávia; Kangussu, Lucas M; Moreira, Fabrício A; Santos, Robson A S; Aguiar, Daniele C; Campagnole-Santos, Maria José

    2016-07-01

    Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain. Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioural responses. In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depression-like behaviours observed in transgenic hypertensive (mRen2)27 rats (TGRs). We also hypothesized that Ang-(1-7) could be involved in the anxiolytic-like effect induced by ACE (angiotensin-converting enzyme) treatment in these hypertensive rats. Therefore, TGRs and Sprague-Dawley rats were subjected to the Elevated Plus Maze (EPM) test, Forced Swimming Test (FST) and Novelty Suppressed Feeding (NSF). TGRs presented a decreased percentage of entries in the open arms of the EPM test, a phenotype reversed by systemic treatment with enalapril or intracerebroventricular infusion of Ang-(1-7). It is interesting that pre-treatment with A779, a selective Mas receptor antagonist, prevented the anxiolytic-like effect induced by the ACE inhibitor. In the NSF test, TGRs showed increased latency to eating, an indicative of a higher aversion in response to a new environment. These animals also showed increased immobility in the FST. Again, Ang-(1-7) reversed this phenotype. Thus, our data showed that Ang-(1-7) can modulate anxiety- and depression-like behaviours in TGRs and warrant further investigation as a new therapy for certain psychiatric disorders. PMID:27129185

  7. Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats.

    Topinka, J; Loli, P; Hurbáková, M; Kováciková, Z; Volkovová, K; Wolff, T; Oesterle, D; Kyrtopoulos, S A; Georgiadis, P

    2006-03-20

    In an attempt to examine the interaction of man-made mineral fibres with benzo[a]pyrene (B[a]P), homozygous X-lacI transgenic F344 rats were intratracheally treated with rock (stone) wool RWI and glass wool MMVF 10 fibres together with B[a]P. To analyze the induction of gene mutations by fibres and B[a]P in lung, single doses of 1 and 2 mg fibres/animal or multiple doses of 2 mg fibres/animal were administered weekly on 4 consecutive weeks (total dose 8 mg/animal). B[a]P (10 mg/animal) was administered either simultaneously with fibres (for single dose treatment with fibres) or together with the last fiber treatment (for multiple dose treatment with fibres). Animals were scarified 4 weeks after the last treatment. Benzo[a]pyrene administered simultaneously with RW1 fibres exhibited a strong synergistic effect on mutagenicity, the observed mutant frequency (MF) being more than three-fold higher than the net sum of the MF induced after separate administration of both agents. Our data suggest that DNA adducts induced by simultaneous B[a]P and fiber treatment lead to a strong increase in mutatant frequencies. PMID:16375931

  8. Transgenic Animals.

    Jaenisch, Rudolf

    1988-01-01

    Describes three methods and their advantages and disadvantages for introducing genes into animals. Discusses the predictability and tissue-specificity of the injected genes. Outlines the applications of transgenic technology for studying gene expression, the early stages of mammalian development, mutations, and the molecular nature of chromosomes.…

  9. Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats

    Repunte-Canonigo, Vez; Lefebvre, Celine; George, Olivier; Kawamura, Tomoya; Morales, Marisela; Koob, George F.; Califano, Andrea; Masliah, Eliezer; Sanna, Pietro Paolo

    2014-01-01

    Background A thorough investigation of the neurobiology of HIV-induced neuronal dysfunction and its evolving phenotype in the setting of viral suppression has been limited by the lack of validated small animal models to probe the effects of concomitant low level expression of multiple HIV-1 products in disease-relevant cells in the CNS. Results We report the results of gene expression profiling of the hippocampus of HIV-1 Tg rats, a rodent model of HIV infection in which multiple HIV-1 protei...

  10. Lesion-dependent regulation of transgene expression in the rat brain using a human glial fibrillary acidic protein-lentiviral vector.

    Jakobsson, Johan; Georgievska, Biljana; Ericson, Cecilia; Lundberg, Cecilia

    2004-01-01

    The ability to regulate transgene expression will be crucial for development of gene therapy to the brain. The most commonly used systems are based on a transactivator in combination with a drug, e.g. the tetracycline-regulated system. Here we describe a different method of transgene regulation by the use of the human glial fibrillary acidic protein (GFAP) promoter. We constructed a lentiviral vector that directs transgene expression to astrocytes. Using toxin-induced lesions we investigated ...

  11. Nogo-A-deficient transgenic rats show deficits in higher cognitive functions, decreased anxiety and altered circadian activity patterns

    Tomas Petrasek

    2014-03-01

    Full Text Available Decreased levels of Nogo-A dependent signaling have been shown to affect behavior and cognitive functions. In Nogo-A knockout and knock-down laboratory rodents, behavioral alterations were observed, possibly corresponding with human neuropsychiatric diseases of neurodevelopmental origin, particularly schizophrenia. This study offers further insight into behavioral manifestations of Nogo-A knockdown in laboratory rats, focusing on spatial and non-spatial cognition, anxiety levels, circadian rhythmicity and activity patterns. Demonstrated is an impairment of cognitive functions and behavioral flexibility in a spatial active avoidance task, while non-spatial memory in a step-through avoidance task was spared. No signs of anhedonia, typical for schizophrenic patients, were observed in the animals. Some measures indicated lower anxiety levels in the Nogo-A deficient group. Circadian rhythmicity in locomotor activity was preserved in the Nogo-A-knockout rats and their circadian period (tau did not differ from controls. However, daily activity patterns were slightly altered in the knockdown animals. We conclude that a reduction of Nogo-A levels induces changes in CNS development, manifested as subtle alterations in cognitive functions, emotionality and activity patterns.

  12. Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats

    2014-01-01

    Background A thorough investigation of the neurobiology of HIV-induced neuronal dysfunction and its evolving phenotype in the setting of viral suppression has been limited by the lack of validated small animal models to probe the effects of concomitant low level expression of multiple HIV-1 products in disease-relevant cells in the CNS. Results We report the results of gene expression profiling of the hippocampus of HIV-1 Tg rats, a rodent model of HIV infection in which multiple HIV-1 proteins are expressed under the control of the viral LTR promoter in disease-relevant cells including microglia and astrocytes. The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analysis. Gene expression changes observed are consistent with astrogliosis and microgliosis and include evidence of inflammation and cell proliferation. Among the genes with increased expression in HIV-1 Tg rats was the interferon stimulated gene 15 (ISG-15), which was previously shown to be increased in the cerebrospinal fluid (CSF) of HIV patients and to correlate with neuropsychological impairment and neuropathology, and prostaglandin D2 (PGD2) synthase (Ptgds), which has been associated with immune activation and the induction of astrogliosis and microgliosis. GSEA-based pathway analysis highlighted a broad dysregulation of genes involved in neuronal trophism and neurodegenerative disorders. Among the latter are genesets associated with Huntington’s disease, Parkinson’s disease, mitochondrial, peroxisome function, and synaptic trophism and plasticity, such as IGF, ErbB and netrin signaling and the PI3K signal transduction pathway, a mediator of neural plasticity and of a vast array of trophic signals. Additionally, gene expression analyses also show altered lipid metabolism and peroxisomes dysfunction. Supporting the functional significance of these gene expression alterations, HIV-1 Tg rats showed working memory impairments in spontaneous alternation behavior in the T-Maze, a

  13. Potential subchronic food safety of the stacked trait transgenic maize GH5112E-117C in Sprague-Dawley rats.

    Han, Shiwen; Zou, Shiying; He, Xiaoyun; Huang, Kunlun; Mei, Xiaohong

    2016-08-01

    The food safety of stacked trait genetically modified (GM) maize GH5112E-117C containing insect-resistance gene Cry1Ah and glyphosate-resistant gene G2-aroA was evaluated in comparison to non-GM Hi-II maize fed to Sprague-Dawley rats during a 90-day subchronic feeding study. Three different dietary concentrations (12.5, 25 and 50 %, w/w) of the GM maize were used or its corresponding non-GM maize. No biologically significant differences in the animals' clinical signs, body weights, food consumption, hematology, clinical chemistry, organ weights and histopathology were found between the stacked trait GM maize groups, and the non-GM maize groups. The results of the 90-day subchronic feeding study demonstrated that the stacked trait GM maize GH5112E-117C is as safe as the conventional non-GM maize Hi-II. PMID:26919987

  14. Sub-Chronic Toxicity Study of Transgenic Cottonseed in SD Rats%转基因棉籽亚慢性毒性的研究

    邱忠礼; 孙娜; 王静; 周催; 车会莲

    2011-01-01

    Objective: To monitor the effects of genetically modified cottonseed on nutritional status, physiological and biochemical sub-chr- onic index in rats.Methods: A total of 140 six to eight - week-old SPF SD rats (male and female,half) were randomly divided into 7 groups, continuously feeding the forage containing 5%, 2.5% and 1.25% normal cottonseed and transgenic cottonseed as well as basal forage for 30 days,and then measuring indicators of body weight, food efficiency,blood routine and blood biochemical parameters.Results: All the animals grow well and there is no poisoning and dead phenomenon during experimental time.Indicators between experimental and control group show no significant difference (P≥ 0.05).Conclusions: The study did not find genetically modified cotton seeds has sub-chronic toxicity in experimental animals.%目的:转基因棉籽对SD大鼠亚慢性毒性的研究.方法:选取出生6-8周的SPF级SD大鼠140只,雌雄各半,按体重随机分成7组,分别连续饲喂含普通棉籽5%、2.5%和1.25%的饲料和含转基因棉籽5%、2.5%和1.25%的饲料以及基础饲料30天.实验过程中监测动物体重、进食量和进水量,结束后分别测定各组动物的血常规、血生化、脏体指数等指标.结果:实验期间各组动物均生长发育良好,无中毒死亡现象发生.实验组实验动物的各项指标与对照组相比,无显著性差异(P≥0.05).结论:本研究未发现转基因棉籽对实验动物有亚慢性毒性.

  15. Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1-7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats.

    Husková, Zuzana; Kopkan, Libor; Červenková, Lenka; Doleželová, Šárka; Vaňourková, Zdeňka; Škaroupková, Petra; Nishiyama, Akira; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Kramer, Herbert J; Červenka, Luděk

    2016-04-01

    The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin-converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 μg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis. PMID:26833491

  16. The colitis-associated transcriptional profile of commensal Bacteroides thetaiotaomicron enhances adaptive immune responses to a bacterial antigen.

    Jonathan J Hansen

    Full Text Available BACKGROUND: Inflammatory bowel diseases (IBD may be caused in part by aberrant immune responses to commensal intestinal microbes including the well-characterized anaerobic gut commensal Bacteroides thetaiotaomicron (B. theta. Healthy, germ-free HLA-B27 transgenic (Tg rats develop chronic colitis when colonized with complex gut commensal bacteria whereas non-transgenic (nTg rats remain disease-free. However, the role of B. theta in causing disease in Tg rats is unknown nor is much known about how gut microbes respond to host inflammation. METHODS: Tg and nTg rats were monoassociated with a human isolate of B. theta. Colonic inflammation was assessed by histologic scoring and tissue pro-inflammatory cytokine measurement. Whole genome transcriptional profiling of B. theta recovered from ceca was performed using custom GeneChips and data analyzed using dChip, Significance Analysis of Microarrays, and Gene Set Enrichment Analysis (GSEA software. Western Blots were used to determine adaptive immune responses to a differentially expressed B. theta gene. RESULTS: B. theta monoassociated Tg rats, but not nTg or germ-free controls, developed chronic colitis. Transcriptional profiles of cecal B. theta were significantly different in Tg vs. nTg rats. GSEA revealed that genes in KEGG canonical pathways involved in bacterial growth and metabolism were downregulated in B. theta from Tg rats with colitis though luminal bacterial concentrations were unaffected. Bacterial genes in the Gene Ontology molecular function "receptor activity", most of which encode nutrient binding proteins, were significantly upregulated in B. theta from Tg rats and include a SusC homolog that induces adaptive immune responses in Tg rats. CONCLUSIONS: B. theta induces colitis in HLA-B27 Tg rats, which is associated with regulation of bacterial genes in metabolic and nutrient binding pathways that may affect host immune responses. These studies of the host-microbial dialogue may lead to

  17. Reactive arthritis.

    Keat, A

    1999-01-01

    Reactive arthritis is one of the spondyloarthropathy family of clinical syndromes. The clinical features are those shared by other members of the spondyloarthritis family, though it is distinguished by a clear relationship with a precipitating infection. Susceptibility to reactive arthritis is closely linked with the class 1 HLA allele B27; it is likely that all sub-types pre-dispose to this condition. The link between HLA B27 and infection is mirrored by the development of arthritis in HLA B27-transgenic rats. In this model, arthritis does not develop in animals maintained in a germ-free environment. Infections of the gastrointestinal, genitourinary and respiratory tract appear to provoke reactive arthritis and a wide range of pathogens has now been implicated. Although mechanistic parallels may exist, reactive arthritis is distinguished from Lyme disease, rheumatic fever and Whipple's disease by virtue of the distinct clinical features and the link with HLA B27. As in these conditions both antigens and DNA of several micro-organisms have been detected in joint material from patients with reactive arthritis. The role of such disseminated microbial elements in the provocation or maintenance of arthritis remains unclear. HLA B27-restricted T-cell responses to microbial antigens have been demonstrated and these may be important in disease pathogenesis. The importance of dissemination of bacteria from sites of mucosal infection and their deposition in joints has yet to be fully understood. The role of antibiotic therapy in the treatment of reactive arthritis is being explored; in some circumstances, both the anti-inflammatory and anti-microbial effects of certain antibiotics appear to be valuable. The term reactive arthritis should be seen as a transitory one, reflecting a concept which may itself be on the verge of replacement, as our understanding of the condition develops. Nevertheless it appropriately describes arthritis that is associated with demonstrable

  18. Peptide binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes, and include HLA-B27-like alleles

    Mothé, Bianca R.; Southwood, Scott; Sidney, John; English, A. Michelle; Wriston, Amanda; Hoof, Ilka; Shabanowitz, Jeffrey; Hunt, Donald F.; Sette, Alessandro

    2013-01-01

    Chinese rhesus macaques are of particular interest in SIV/HIV research as these animals have prolonged kinetics of disease progression to AIDS, compared to their Indian counterparts, suggesting that they may be a better model for HIV. Nevertheless, the specific mechanism(s) accounting for these kinetics remains unclear. The study of Major Histocompatibility Complex (MHC) molecules, including their MHC:peptide binding motifs, provides valuable information for measuring cellular immune response...

  19. Post chlamydial reactive arthritis in a case of Vogt-Kayanagi-Harada syndrome (VKH) with negative HLA-B27. An assocation of just coincidence

    Emad, Y.; Ragab, Y.; Rasker, J.J.

    2013-01-01

    Background Vogt-Koyanagi-Harada (VKH) syndrome is a multisystem disorder characterized by granulomatous panuveitis with exudative retinal detachments that is often associated with neurologic and cutaneous manifestations. Aim of the work The aim of this case report is to describe a rare case with Vo

  20. ERAP1 genetic variations associated with HLA-B27 interaction and disease severity of syndesmophytes formation in Taiwanese ankylosing spondylitis

    Wang, Chin-Man; Ho, Huei-Huang; Chang, Su-Wei; Wu, Yeong-Jian Jan; Lin, Jing-Chi; Chang, Pi-Yueh; Wu, Jianming; Chen, Ji-Yih

    2012-01-01

    Introduction Ankylosing spondylitis (AS) is a familial, heritable disease specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to be associated with AS in several ethnic populations. The aim of this study was to investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated with AS susceptibility and disease severity in Taiwanese. Methods Four ERAP1 SNPs (rs27037, rs27980,...

  1. Ectopic Germinal Centers and IgG4-Producing Plasmacytes Observed in Synovia of HLA-B27+ Ankylosing Spondylitis Patients with Advanced Hip Involvement

    Xiugao Feng

    2015-01-01

    Full Text Available Introduction. Ectopic lymphoid neogenesis and the presence of IgG4-positive plasmacytes have been confirmed in chronic inflammatory sclerosing diseases. This study aims to investigate hip synovial tissues of ankylosing spondylitis (AS patients for IgG4-positive plasma cells and ectopic lymphoid tissues with germinal centers (GCs. Methods. Synovial samples were collected from 7 AS patients who received total hip replacement and were evaluated using immunohistochemistry for the presence of CD20+ B-cells, CD3+ T-cells, CD21+ follicular dendritic cells (FDC, and CD38+ plasma cells. Furthermore, immunoglobulin G (IgG and IgG4, IgA, IgM, and complement components C3d and C4d in synovia were evaluated. Both synovial CD21+ FDCs and IgG4-producing plasmacytes were analyzed. Results. All seven patients had severe fibrosis. Massive infiltrations of lymphocytes were found in 5 out of 7 patients’ synovia. Ectopic lymphoid tissues with CD21+ FDC networks and IgG4-positive plasma cells were observed coincidentally in two patients’ synovia. Conclusion. The pathophysiological mechanism of AS patients’ hip damage might be related to the coincidental presence of ectopic lymphoid tissue with FDCs network and IgG4-positive plasma cells identified here for the first time in AS patients’ inflamed synovial tissue.

  2. HLA-B73: An atypical HLA-B molecule carrying a Bw6-epitope motif variant and a B pocket identical to HLA-B27

    Vilches, C.; Pablo, R. de; Herrero, M.J.; Moreno, M.E.; Kreisler, M. [Hospital Puerta de Hierro, Madrid (Spain)

    1994-12-31

    HLA-B73, first described by Mayr and Kirnbauer (1981), is a poorly characterized allospecificity, serologically related to the B7-CREG. We polymerase chain reaction-amplified, cloned and sequenced the HLA-B alleles of the B-LCL LE023, established from a Spanish Caucasoid individual expressing HLA-B73. 5 refs., 2 figs.

  3. Interaction pattern of Arg 62 in the A-pocket of differentially disease-associated HLA-B27 subtypes suggests distinct TCR binding modes.

    Elisa Nurzia

    Full Text Available The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL and TIS (RRLPIFSRL, and the viral peptides pLMP2 (RRRWRRLTV and NPflu (SRYWAIRTR. Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K and non-conservative (R62A B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype.

  4. APPswe/PS1 dE9/TAU 三转基因阿尔兹海默病大鼠模型的建立%Establishment of APPswe/PS1 dE9/TAU triple transgenic rat model of alzheimer disease

    张丽; 陈炜; 张旭; 孙彩显; 张连峰

    2014-01-01

    目的:大鼠的大脑比小鼠更大,是研究神经系统的重要模型。建立APPswe/PS1dE9/TAU三转基因大鼠,发展能更全面表现人类阿尔兹海默病表型的动物模型。方法构建人PrP-hAPP695 K595N/M596L、PrP-hPS1dE9和PDGF-TAU转基因表达载体,显微注射法制备转基因大鼠。 PCR法鉴定转基因首建鼠及其子代基因型。 Western blot检测转基因大鼠脑组织中人APP、PS1和TAU蛋白的表达。 Morris水迷宫检测6月龄三转基因大鼠学习记忆能力改变。 APP、PHF-TAU免疫组织化学染色观察三转基因大鼠脑组织APP及TAU的表达。结果得到1个同时高表达人APP、PS1和TAU三个基因的转基因大鼠品系。转基因大鼠6月龄已经出现显著的行为学改变:学习记忆能力下降,病理学改变表现为过度磷酸化TAU增多和神经元胞浆内Aβ表达异常增加。结论成功建立了APPswe/PS1dE9/TAU三转AD大鼠,可做为新一代工具动物模型用于基础医学和AD转化医学研究。%Objective To develop a model that could roundly show the phenotypes of human alzheimer disease (AD), the triple-transgenic rat model harboring APP(Swe), PS1dE9, and TAU transgenes was established in view of the advantage of rat as an important animal model on the research of nerve system .Methods APPswe/PS1dE9/TAU triple transgenic rat AD rats were generated on a SD background by co-injecting rat pronuclei with two human genes driven by the mouse prion promoter:‘Swedish’ mutant human APP (APPsw) and exon 9 mutant human presenilin-1 (PS1dE9) and human microtubule-associated protein tau gene under the control of PDGF promoter .Transgene integration was confirmed by genotyping and expression levels were evaluated by western blot ( WB ) of brain homogenates .The pathological changes were detected by human Abeta, TAU and Phospho-PHF-TAU immunohistochemistry staining (IHC).The behavioral and cognitive changes were evaluated by Morris water maze .Results

  5. Neuroanatomy and transgenic technologies

    This is a short review that introduces recent advances of neuroanatomy and transgenic technologies. The anatomical complexity of the nervous system remains a subject of tremendous fascination among neuroscientists. In order to tackle this extraordinary complexity, powerful transgenic technologies a...

  6. Enhancement of cell-specific transgene expression from a Tet-Off regulatory system using a transcriptional amplification strategy in the rat brain

    Liu, Beihui; Wang, Shu; Brenner, Michael; Paton, Julian FR; Kasparov, Sergey

    2008-01-01

    Background The Tet-Off system uses a tetracycline-controlled transactivator protein (tTA) and a tetracycline-responsive promoter element (TRE) to regulate expression of a target gene. This system can be used to achieve regulatable transgene expression in specific cell types by employing a cell-specific promoter to drive tTA expression. Wide applications of this attractive approach are, however, hindered by relatively weak transcriptional activity of most cell-specific promoters. We report her...

  7. Design and Management of a Transgenic Facility

    Bob Springsteen

    2001-01-01

    @@ In 1965, I was given the opportunity to manage a research animal colony. At that time, the animal colony consisted of numerous species, such as primates, dogs, cats, rab bits, guinea pigs, hamsters, rats, mice, and some farm animals as well. Over the years,this menagerie was reduced to mice and rab bits. The animal facility now houses 8 000mice, of which 80% are transgenics. In approximately six years, transgenic mice have become the mainstay of the Berkeley Lab animal facility, and this population continues to grow.

  8. The optimal dose and reaction time of HLA-B27 antibody in flow cytometry%流式细胞术检测 HLA-B27最佳抗体剂量与作用时间研究

    李娜; 高文波; 周玉明

    2015-01-01

    目的:探讨流式细胞术检测人类白细胞抗原B27(HLA‐B27)时所用的最佳抗体剂量与作用时间。方法取52例强直性脊柱炎患者全血,根据HLA‐B27抗体剂量不同分为5、10μL两组,分别避光静置5、10、15 min ,溶血后上机检测 HLA‐B27水平。结果5μL抗体组不同反应时间HLA‐B27阳性率分别为(84.16±1.21)%、(94.81±1.33)%、(94.1±1.26)%;10μL抗体组不同反应时间 HLA‐B27阳性率分别为(85.4±1.27)%、(96.76±1.31)%、(95.36±1.45)%;10μL抗体组 HLA‐B27检测结果高于5μL抗体组,差异有统计学意义(F=90.08,P<0.05);抗体反应10、15 min HLA‐B27检测结果高于抗体反应5 min检测结果,差异有统计学意义(F=60.25,P<0.05);抗体反应10 min HLA‐B27检测结果与抗体反应15 min检测结果比较差异无统计学意义(F=1.08,P>0.05)。结论 HLA‐B27抗体剂量10μL ,反应10 min为最佳实验方案;HLA‐B27抗体剂量、反应时间无交互作用。%Objective To study the optimal dose and reaction time of human leukocyte antigen B27(HLA‐B27)antibody in flow cytometry .Methods Take 52 cases of whole blood in patients with ankyl‐osing spondylitis(AS) .According to HLA‐B27 antibody doses ,samples were divided into two groups:5 μL group and 10 μL group .HLA‐B27‐positive rate were tested after 5 ,10 ,15 min , respectively .Results The HLA‐B27 positive rate of 5 μL group at different reaction time were (84 .16 ± 1 .21)% ,(94 .81 ± 1 .33)% ,(94 .10 ± 1 .26)% ;the positive rate of 10 μL group at different reaction time were (85 .40 ± 1 .27)% ,(96 .76 ± 1 .31)% , (95 .36 ± 1 .45)% .The positive rate of HLA‐B27 in 10 μL group was higher than 10 μL group(F=90 .08 ,P0 .05) .Conclusion The opti‐mal dose and reaction time of HLA‐B27 antibody in flow cytometry are 10μL and 10 min;There is not any interaction between anti‐body dose and the reaction time of HLA‐B27 antibody .

  9. Administration of 4-(α-L-Rhamnosyloxy)-benzyl Isothiocyanate Delays Disease Phenotype in SOD1G93A Rats: A Transgenic Model of Amyotrophic Lateral Sclerosis

    De Nicola, Gina Rosalinda; Mazzon, Emanuela

    2015-01-01

    4-(α-L-Rhamnosyloxy)-benzyl glucosinolate (glucomoringin, GMG) is a compound found in Moringa oleifera seeds. Myrosinase-catalyzed hydrolysis at neutral pH of GMG releases the biologically active compound 4-(α-L-rhamnosyloxy)-benzyl isothiocyanate (GMG-ITC). The present study was designed to test the potential therapeutic effectiveness of GMG-ITC to counteract the amyotrophic lateral sclerosis (ALS) using SOD1tg rats, which physiologically develops SOD1G93A at about 16 weeks of life, and can be considered a genetic model of disease. Rats were treated once a day with GMG (10 mg/Kg) bioactivated with myrosinase (20 µL/rat) via intraperitoneal (i.p.) injection for two weeks before disease onset and the treatment was prolonged for further two weeks before the sacrifice. Immune-inflammatory markers as well as apoptotic pathway were investigated to establish whether GMG-ITC could represent a new promising tool in clinical practice to prevent ALS. Achieved data display clear differences in molecular and biological profiles between treated and untreated SOD1tg rats leading to guessing that GMG-ITC can interfere with the pathophysiological mechanisms at the basis of ALS development. Therefore, GMG-ITC produced from myrosinase-catalyzed hydrolysis of pure GMG could be a candidate for further studies aimed to assess its possible use in clinical practice for the prevention or to slow down this disease. PMID:26075221

  10. Administration of 4-(α-L-rhamnosyloxy)-benzyl isothiocyanate delays disease phenotype in SOD1(G93A) rats: a transgenic model of amyotrophic lateral sclerosis.

    Galuppo, Maria; Giacoppo, Sabrina; Iori, Renato; De Nicola, Gina Rosalinda; Bramanti, Placido; Mazzon, Emanuela

    2015-01-01

    4-(α-L-Rhamnosyloxy)-benzyl glucosinolate (glucomoringin, GMG) is a compound found in Moringa oleifera seeds. Myrosinase-catalyzed hydrolysis at neutral pH of GMG releases the biologically active compound 4-(α-L-rhamnosyloxy)-benzyl isothiocyanate (GMG-ITC). The present study was designed to test the potential therapeutic effectiveness of GMG-ITC to counteract the amyotrophic lateral sclerosis (ALS) using SOD1tg rats, which physiologically develops SOD1(G93A) at about 16 weeks of life, and can be considered a genetic model of disease. Rats were treated once a day with GMG (10 mg/Kg) bioactivated with myrosinase (20 µL/rat) via intraperitoneal (i.p.) injection for two weeks before disease onset and the treatment was prolonged for further two weeks before the sacrifice. Immune-inflammatory markers as well as apoptotic pathway were investigated to establish whether GMG-ITC could represent a new promising tool in clinical practice to prevent ALS. Achieved data display clear differences in molecular and biological profiles between treated and untreated SOD1tg rats leading to guessing that GMG-ITC can interfere with the pathophysiological mechanisms at the basis of ALS development. Therefore, GMG-ITC produced from myrosinase-catalyzed hydrolysis of pure GMG could be a candidate for further studies aimed to assess its possible use in clinical practice for the prevention or to slow down this disease. PMID:26075221

  11. A 90-Day Toxicology Study of Transgenic Rice Expressing Lysine-Rich Protein Fusion Gene in Sprague-Dawley Rats%转高赖氨酸融合蛋白基因大米喂养SD大鼠90天试验研究

    董英; 施卫东; 周兴华; 张奕; 王云; 肖香

    2011-01-01

    [Objective] Rats were fed by transgenic rice expressing lysine-rich protein fusion gene to study if the transgenic rice possesses potential toxic or adverse effects. [Method] According to the composition of the transgenic GL gene rice and its parental rice, a nutritionally balanced purified diet with 70% transgenic GL gene rice or 70% parental rice was prepared. And the nutrition of the diet was the same as the control diet. Sixty weanling Sprague-Dawley rats were divided into three groups according to their sex and weight respectively: transgenic rice group, nontransgenic rice group, and control group. They were fed with corresponding diet for 90 days. Indicators including body weight, feed volume, feed utilization rate, blood routine test, blood biochemistry test, urinary routine test, relative organ weights and organ histopathological examinations were observed. [Result] No significant differences were found between transgenic rice group and non-transgenic rice group (P>0.05) and no histopathological damage was detected. Female feed volume and CHOL of male serum of terminal experiment in transgenic rice group were lower than those of control group (P0.05);转GL基因大米组与对照组相比,转GL基因大米雌性组进食量、雄性组试验末期血清中CHOL显著低于对照组(P<0.05),而转GL基因大米雌性组食物利用率、雄性组试验末期全血中MCV、雄性组试验中期血清中AST、雄性组试验末期血清中AST/ALT和P显著高于对照组(P<0.05),但这些数据并没有显示出生物学意义上的显著性差异,而且血常规与血生化指标均在正常值范围内.[结论]转GL基因大米对大鼠生长发育无明显不良影响,转GL基因大米和其亲本大米对大鼠有同等的食用安全性.

  12. Generation of Transgenic Mice

    Cho, Andrew; Haruyama, Naoto; Kulkarni, Ashok B.

    2009-01-01

    This unit describes detailed step-by-step protocols, reagents, and equipment required for successful generation of transgenic mice using pronuclear injection. The experimental methods and practical tips given here will help guide beginners in understanding what is required and what to avoid in these standard protocols for efficiently generating transgenic mice.

  13. Epithelial cell differentiation in normal and transgenic mouse intestinal isografts

    1991-01-01

    Transgenes consisting of segments of the rat liver fatty acid-binding protein (L-FABP) gene's 5' non-transcribed domain linked to the human growth hormone (hGH) gene (minus its regulatory elements) have provided useful tools for analyzing the mechanisms that regulate cellular and spatial differentiation of the continuously renewing gut epithelium. We have removed the jejunum from normal and transgenic fetal mice before or coincident with, cytodifferentiation of its epithelium. These segments ...

  14. Can transgenic rice cause ecological risks through transgene escape?

    2003-01-01

    Alien transgene escape from genetically engineered rice to non-transgenic varieties or close wild relatives (including weedy rice) may lead to unpredictable ecological risks. However, for transgene escape to occur three conditions need to be met: (i) spatially, transgenic rice and its non-transgenic counterparts or wild relatives should have sympatric distributions; (ii) temporally, the flowering time of transgenic rice and the non-transgenic varieties or wild relatives should overlap; and (iii) biologically, transgenic rice and its wild relative species should have such a sufficiently close relationship that their interspecific hybrids can have normal generative reproduction. This paper presents research data on the geographic distribution, flowering habits, interspecific hybridization, and gene flow of cultivated rice (Oryza sativa) and its closely related wild relatives containing the AA genome. The objective is to estimate the possibility of transgene escape to non-transgenic rice varieties and wild relatives of rice, which may result in unpredictable ecological risks.

  15. Dual transplantation of human neural stem cells into cervical and lumbar cord ameliorates motor neuron disease in SOD1 transgenic rats

    Xu, Leyan; Shen, Peilin; Hazel, Thomas; Johe, Karl; Koliatsos, Vassilis E.

    2011-01-01

    Stem cells provide novel sources of cell therapies for motor neuron disease that have recently entered clinical trials. In the present study, we transplanted human neural stem cells (NSCs) into the ventral horn of both the lumbar (L4–L5) and cervical (C4–C5) protuberance of SOD G93A rats, in an effort to test the feasibility and general efficacy of a dual grafting paradigm addressing several muscle groups in the front limbs, hind limbs and the respiratory apparatus. Transplantation was done p...

  16. Transgenic mice: beyond the knockout

    Miller, R. Lance

    2010-01-01

    Transgenic mice have had a tremendous impact on biomedical research. Most researchers are familiar with transgenic mice that carry Cre recombinase (Cre) and how they are used to create conditional knockouts. However, some researchers are less familiar with many of the other types of transgenic mice and their applications. For example, transgenic mice can be used to study biochemical and molecular pathways in primary cultures and cell suspensions derived from transgenic mice, cell-cell interac...

  17. Transgene mus som sygdomsmodeller

    Schuster, Mikkel Bruhn; Porse, Bo Torben

    2003-01-01

    Transgenic animal models have proven to be useful tools in understanding both basic biology and the events associated with disease. Recent technical advances in the area of genomic manipulation in combination with the availability of the human and murine genomic sequences now allow the precise...... tailoring of the mouse genome. In this review we describe a few systems in which transgenic animal models have been employed for the purpose of studying the etiology of human diseases. Udgivelsesdato: 2003-Feb-17...

  18. Calcium electrotransfer for termination of transgene expression in muscle

    Hojman, Pernille; Spanggaard, Iben; Olsen, Caroline Holkman;

    2011-01-01

    clinical grade calcium solution (20 μl, 168 mM) was injected into transfected mouse or rat tibialis cranialis muscle. Ca(2+) uptake was quantified using calcium 45 ((45)Ca), and voltage and time between injection and pulsation were varied. Extinction of transgene expression was investigated by using both...

  19. Transgenic mice susceptible to poliovirus.

    S. Koike; Taya, C; Kurata, T; Abe, S.; Ise, I; Yonekawa, H; Nomoto, A

    1991-01-01

    Poliovirus-sensitive transgenic mice were produced by introducing the human gene encoding cellular receptors for poliovirus into the mouse genome. Expression of the receptor mRNAs in tissues of the transgenic mice was analyzed by using RNA blot hybridization and the polymerase chain reaction. The human gene is expressed in many tissues of the transgenic mice just as in tissues of humans. The transgenic mice are susceptible to all three poliovirus serotypes, and the mice inoculated with poliov...

  20. Transgene Stacking in Cotton Improvement

    2008-01-01

    To date,more and more transgenic varieties of upland cotton(Gossypium hirsutum L.) generated with transgenes,which derived from varies of alien species,are playing important role in agricultural production.Stacking of multi-transgenes has a potential for combining all the merits of distinct

  1. Transgenic Farm Animals

    The development of recombinant DNA technology has enabled scientists to isolate single genes, analyze and modify their nucleotide structure(s), make copies of these isolated genes, and insert copies of these genes into the genome of plants and animals. The transgenic technology of adding genes to li...

  2. Transgenics in crops

    Li, Y.; Wu, Y. H.; McAvoy, R.; Duan, H.

    2001-01-01

    With rapid world population growth and declining availability of fresh water and arable land, a new technology is urgently needed to enhance agricultural productivity. Recent discoveries in the field of crop transgenics clearly demonstrate the great potential of this technology for increasing food production and improving food quality while preserving the environment for future generations. In this review, we briefly discuss some of the recent achievements in crop improvement that have been made using gene transfer technology.

  3. Retinoblastoma in transgenic mice

    Windle, J J; Albert, D. M.; O'Brien, J. M.; Marcus, D. M.; Disteche, Ch.M.; Bernards, R.A.; Mellon, P L

    1990-01-01

    Retinoblastoma, a malignancy of the eye occurring in young children, has been widely studied as a model for genetic predisposition to cancer. This disease is caused by mutations in both alleles of an anti-oncogene (the retinoblastoma gene, Rb) that inactivate or eliminate the Rb encoded protein, pl05rb. Here we report that expression of a viral oncogene, the simian virus 40 T antigen, in the retina of transgenic mice produces heritable ocular tumours with histological, ultrastructural and imm...

  4. Transgenic algae engineered for higher performance

    Unkefer, Pat J; Anderson, Penelope S; Knight, Thomas J

    2014-10-21

    The present disclosure relates to transgenic algae having increased growth characteristics, and methods of increasing growth characteristics of algae. In particular, the disclosure relates to transgenic algae comprising a glutamine phenylpyruvate transaminase transgene and to transgenic algae comprising a glutamine phenylpyruvate transaminase transgene and a glutamine synthetase.

  5. Transgenics, agroindustry and food sovereignty

    Xavier Alejandro León Vega

    2014-01-01

    Food sovereignty has been implemented constitutionally in Ecuador; however, many of the actions and policies are designed to benefit the dominant model of food production, based in agroindustry, intensive monocultures, agrochemicals and transgenics. This article reflects upon the role of family farming as a generator of food sovereignty, and secondly the threat to them by agroindustry agriculture based in transgenic. The role played by food aid in the introduction of transgenic in Latin Ameri...

  6. Cryopreservation of Xenopus transgenic lines.

    Buchholz, Daniel R; Fu, Liezhen; Shi, Yun-Bo

    2004-01-01

    Xenopus laevis has been widely used for molecular, cellular, and developmental studies. With the development of the sperm-mediated transgenic method, it is now possible to study gene function during vertebrate development by using this popular model. On the other hand, like other animal species, it is labor intensive, and the maintenance of transgenic lines is expensive. In this article, we investigated the possibility of using sperm-cryopreservation as a means to preserve transgenic frog lines. We demonstrated that cryopreserved sperms are viable but not fertile under our in vitro fertilization (IVF) conditions. However, by microinjecting cryopreserved sperm nuclei, we successfully regenerated a transgenic line carrying a double promoter transgene construct, where the marker gene encoding the green fluorescent protein (GFP) is driven by the gamma-crystallin gene promoter and a gene of interest, encoding a fusion protein of GFP with the matrix metalloproteinase stromelysin-3 (ST3-GFP), is driven by a heat shock-inducible promoter. We demonstrated the functional transmission of the ST3-GFP transgene by analyzing the phenotype of the F1 animals after heat-shock to induce its expression. Our method thus provides an inexpensive means to preserve transgenic frog lines and a convenient way for distribution of transgenic lines. Furthermore, the ease with which to microinject nuclei compared to the technically demanding transgenesis procedure with variable outcome should facilitate more laboratories to use transgenic Xenopus laevis for functional studies in vivo. Mol. Reprod. Dev. 67: 65-69, 2004. PMID:14648875

  7. Biosafety assessment of transgenic Bt cotton on model animals

    Sadia Bano

    2016-05-01

    Full Text Available Abstract Background: To know the effects of transgenic crops on soil microorganisms, animals and other expected hazards due to the introduction of GM crops into the environment is critical both scientifically and environmentally. The work was conducted to study the effect of insecticidal Bt protein on Rats and Earthworms. Methods: For this purpose, animals like rat and soil organisms like Earthworm were selected. Rats were selected on the basis of its 95% homology on genomic, cellular and enzymatic level with human while earthworm were preferred on the basis of their direct contact with soil to evaluate the impact of Bt (Cry1AC crop field soil on earthworm, secreted by root exudates of Bt cotton. Several physical, molecular, biochemical and histological analyses were performed on both Rats/Earthworms fed on standard diet (control group as well containing Bt protein (experimental group. Results: Molecular analyses such as immune Dot blot, SDS-PAGE, ELISA and PCR, confirmed the absence of Cry1Ac protein in blood and urine samples of rats, which were fed with Bt protein in their diet. Furthermore, histological studies showed that there was no difference in cellular architecture in liver, heart, kidney and intestine of Bt and non-Bt diet fed rats. To see the effect of Bt on earthworm two different groups were studied, one with transgenic plant field soil supplemented with grinded leaves of cotton and second group with non-Bt field soil. Conclusions: No lethal effects of transgenic Bt protein on the survival of earthworm and rats were observed. Bradford assay, Dipstick assay ELISA demonstrated the absence of Cry1Ac protein in the mid-gut epithelial tissue of earthworm. The results of present study will be helpful in successful deployment and commercial release of genetically modified crop in Pakistan.

  8. Rats

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  9. TL transgenic mouse strains

    As a result of abnormal development of the thymus of these mice, TCR αβ lineage of the T cell differentiation is disturbed and cells belonging to the TCR γδ CD4- CD8- double negative (DN) lineage become preponderant. The γδ DN cells migrate into peripheral lymphoid organs and constitute nearly 50% of peripheral T cells. Immune function of the transgenic mice is severely impaired, indicating that the γδ cells are incapable of participating in these reactions. Molecular and serological analyses of T-cell lymphomas reveal that they belong to the γδ lineage. Tg.Tlaa-3-1 mice should be useful in defining the role of TL in normal and abnormal T cell differentiation as well as in the development of T-cell lymphomas, and further they should facilitate studies on the differentiation and function of γδ T cells. We isolated T3b-TL gene from B6 mice and constructed a chimeric gene in which T3b-TL is driven by the promoter of H-2Kb. With the chimeric gene, two transgenic mouse strains, Tg. Con.3-1 and -2 have been derived in C3H background. Both strains express TL antigen in various tissues including skin. The skin graft of transgenic mice on C3H and (B6 X C3H)F1 mice were rejected. In the mice which rejected the grafts, CD8+TCRαβ cytotoxic T cells (CTL) against TL antigens were recognized. The recognition of TL by CTL did not require the antigen presentation by H-2 molecules. The results indicated that TL antigen in the skin becomes a transplantation antigen and behaves like a typical allogeneic MHC class I antigen. The facts that (B6 X C3H)F1 mice rejected the skin expressing T3b-TL antigen and induced CTL that killed TL+ lymphomas of B6 origin revealed that TL antigen encoded by T3b-TL is recognized as non-self in B6 mice. Experiments are now extended to analyze immune responses to TL antigen expressed on autochthonous T cell lymphomas. (J.P.N.)

  10. [Transgenics without Manichaeism].

    Valle, S

    2000-01-01

    We live in an era characterized by the hegemony of science and technology, an era fraught with questions awaiting answers which would enable a safe and sustainable future for humankind. The development of agro-industrial processes - food products in particular - through recombinant DNA technology has enhanced the profit prospects of the few big biotechnology companies and of large-scale farmers who have access to the latest technological developments. We thus oppose a moratorium on recombinant DNA technology. Moreover, hasty statements about risk-free transgenics may be misleading in the absence of extensive safety tests. There is a pressing need for the establishment of biosafety policy in this country involving the organized civil society and every government agency responsible for monitoring such matters. There is also the need to put in place a bio-surveillance and a code of ethics regarding genetic manipulation. PMID:16680900

  11. COMPARISON TRANSGENIC AND NON-TRANSGENIC MILK QUALITY

    Peter Chrenek

    2012-02-01

    Full Text Available Transgenic founder rabbits carrying a gene construct consisting of a 2.5 kb murine whey acidic protein promoter (mWAP, 7.2 kb of the human clotting factor VIII (hFVIII cDNA and 4.6 kb of 3’ flanking sequences of mWAP gene were crossed for five generations. Transgenic females showed high level of recombinant hFVIII (rhFVIII mRNA expression in biopsed mammary gland tissues. The presence of the mWAP-hFVIII transgene in rabbit genome and secretion of rhFVIII into milk of transgenic females (F1, F2, F3, F4 and F5 generation did not have any adverse phenotypic effect on milk quality.

  12. Transgenics, agroindustry and food sovereignty

    Xavier Alejandro León Vega

    2014-10-01

    Full Text Available Food sovereignty has been implemented constitutionally in Ecuador; however, many of the actions and policies are designed to benefit the dominant model of food production, based in agroindustry, intensive monocultures, agrochemicals and transgenics. This article reflects upon the role of family farming as a generator of food sovereignty, and secondly the threat to them by agroindustry agriculture based in transgenic. The role played by food aid in the introduction of transgenic in Latin America and other regions of the world is also analyzed.

  13. Transgene teknikker erstatter problematisk avl

    Alstrup, Aage Kristian Olsen; Hansen, Axel Kornerup

    2016-01-01

    Dyremodeller har ofte været baseret på avl, der ud fra et alment velfærdsmæssigt synspunkt var problematisk. Transgene teknikker kan ofte forbedre dyrevelfærden ved at erstatte disse traditionelle avlsmetoder.......Dyremodeller har ofte været baseret på avl, der ud fra et alment velfærdsmæssigt synspunkt var problematisk. Transgene teknikker kan ofte forbedre dyrevelfærden ved at erstatte disse traditionelle avlsmetoder....

  14. Heterologous expression in transgenic mosquitoes

    Santhosh P K; Yu hua Deng; Weidong Gu; Xiaoguang Chen

    2010-01-01

    Arthropod-borne diseases such as malaria and dengue virus afflict billions of people worldwide imposing major economic and social burdens. Control of such pathogens is mainly performed by vector management and treatment of affected individuals with drugs. The failure of these conventional approaches due to emergence of insecticide-resistant insects and drug-resistant parasites demonstrate the need of novel and efficacious control strategies to combat these diseases. Genetic modification(GM) of mosquito vectors to impair their ability to be infected and transmit pathogens has emerged as a new strategy to reduce transmission of many vector-borne diseases and deliver public health gains. Several advances in developing transgenic mosquitoes unable to transmit pathogens have gained support, some of them attempt to manipulate the naturally occurring endogenous refractory mechanisms, while others initiate the identification of an exogenous foreign gene which disrupt the pathogen development in insect vectors. Heterologous expression of transgenes under a native or heterologous promoter is important for the screening and effecting of the transgenic mosquitoes. The effect of the transgene on mosquito fitness is a crucial parameter influencing the success of this transgenic approach. This review examines these two aspects and describes the basic research work that has been accomplished towards understanding the complex relation between the parasite and its vector and focuses on recent advances and perspectives towards construction of transgenic mosquitoes refractory to vector-borne disease transmission.

  15. Conditional and targeted overexpression of vascular chymase causes hypertension in transgenic mice

    Ju, Haisong; Gros, Robert; You, Xiaomang; Tsang, Sarah; Husain, Mansoor; Rabinovitch, Marlene

    2001-01-01

    We cloned a rat vascular chymase (RVCH) from smooth muscle cells (SMCs) that converts angiotensin I to II and is up-regulated in SMC from spontaneously hypertensive vs. normotensive rats. To determine whether increased activity of RVCH is sufficient to cause hypertension, transgenic mice were generated with targeted conditional expression of RVCH to SMC, with the use of the tetracycline-controlled transactivator (tTA). We confirmed conditional expression of RVCH by mRNA, protein, and chymase ...

  16. Intracerebral transplants of primary muscle cells: a potential 'platform' for transgene expression in the brain

    Jiao, S.; Schultz, E.; Wolff, J. A.

    1992-01-01

    After the transplantation of rat primary muscle cells into the caudate or cortex of recipient rats, the muscle cells were able to persist for at least 6 months. Muscle cells transfected with expression plasmids prior to transplantation were able to express reporter genes in the brains for at least 2 months. These results suggest that muscle cells might be a useful 'platform' for transgene expression in the brain.

  17. Transgenic agriculture and environmental indicators

    Denize Dias de Carvalho

    2006-12-01

    Full Text Available Despite the rapid diffusion of transgenic crops, there are still few environmental impact studies capable of supplying a conclusive scientific response in regard to its technical and economic advantages and disadvantages. Prospective scenarios were elaborated to assist environmental impact assessment, using techniques derived from SWOT (Strength, Weakness, Opportunity, Threat analysis and the DPSIR (Driving Force – human activity, Pressure, State, Impact, Response model, to evaluate the environmental indicators and the relationship between them. Control and management actions were identified, searching the integration of aspects related to the biotechnology applied to transgenic processes, biodiversity, biosafety and intellectual property. It was demonstrated that the DPSIR model is, in fact, an instrument for integrated environmental assessment and the application of the proposed methodology resulted in favorable indicators to the adoption of transgenic agriculture. The elaborated scenarios are useful to develop an Environmental Management System (EMS to agriculture.

  18. [Transgenic animals and animal welfare

    Reinhardt, Christoph

    1998-01-01

    Under the pressure of a public vote in Switzerland (7 June 1998) on an initiative to ban the production, use and patenting of transgenic animals, their value for biomedical research and development is intensely debated. In addition, the Swiss legislation has adopted (1992) a constitutional obligation to "take into account the dignity of creatures". The term "dignity of creatures", however, can be interpreted in anthropocentric or biocentric ways. The government has now formulated the legal implications of this term for transgenic animals and plants in various laws including the animal and environmental protection laws. This paper gives arguments for a fair evaluation of trangenic animals from an animal welfare point of view where not only the costs of animal suffering must be considered but also the probability of potential benefit for man. A self-confident research community should allow such an evaluation procedure even in view of an outcome which could ban many uses of transgenic animals PMID:11208266

  19. Transgenic woody plants for biofuel

    Wei Tang; Anna Y.Tang

    2014-01-01

    Transgenic trees as a new source for biofuel have brought a great interest in tree biotechnology. Genetically modifying forest trees for ethanol production have advantages in technical challenges, costs, environmental concerns, and financial problems over some of crops. Genetic engineering of forest trees can be used to reduce the level of lignin, to produce the fast-growing trees, to develop trees with higher cellulose, and to allow the trees to be grown more widely. Trees can establish themselves in the field with less care of farmers, compared to most of crops. Transgenic crops as a new source for biofuel have been recently reviewed in several reviews. Here, we overview transgenic woody plants as a new source for biofuel including genetically modified woody plants and environment; main focus of woody plants genetic modifications;solar to chemical energy transfer; cellulose biosynthesis;lignin biosynthesis;and cellulosic ethanol as biofuel.

  20. Persistence, Localization, and External Control of Transgene Expression After Single Injection of Adeno-Associated Virus into Injured Joints

    Lee, Hannah H.; O'Malley, Michael J.; Friel, Nicole A.; Payne, Karin A.; Qiao, Chunping; Xiao, Xiao(Institute for Strings, Cosmology and Astroparticle Physics (ISCAP) and Physics Department, Columbia University, 538 West 120th Street, New York, NY, 10027 U.S.A.); Chu, Constance R.

    2013-01-01

    A single intra-articular injection of adeno-associated virus (AAV) results in stable and controllable transgene expression in normal rat knees. Because undamaged joints are unlikely to require treatment, the study of AAV delivery in joint injury models is crucial to potential therapeutic applications. This study tests the hypotheses that persistent and controllable AAV-transgene expression are (1) highly localized to the cartilage when AAV is injected postinjury and (2) localized to the intra...

  1. Transgenic mouse offspring generated by ROSI

    Moreira, Pedro; Pérez-Cerezales, Serafín; LAGUNA, Ricardo; FERNÁNDEZ-GONZALEZ, Raúl; SANJUANBENITO, Belén Pintado; Gutiérrez-Adán, Alfonso

    2015-01-01

    The production of transgenic animals is an important tool for experimental and applied biology. Over the years, many approaches for the production of transgenic animals have been tried, including pronuclear microinjection, sperm-mediated gene transfer, transfection of male germ cells, somatic cell nuclear transfer and the use of lentiviral vectors. In the present study, we developed a new transgene delivery approach, and we report for the first time the production of transgenic animals by co-...

  2. Temporal Expression of Mutant LRRK2 in Adult Rats Impairs Dopamine Reuptake

    Hongxia Zhou, Cao Huang, Jianbin Tong, Weimin C Hong, Yong-Jian Liu, Xu-Gang Xia

    2011-01-01

    Full Text Available Parkinson's disease (PD results from progressive degeneration of dopaminergic neurons. Most PD cases are sporadic, but some have pathogenic mutation in the individual genes. Mutation of the leucine-rich repeat kinase-2 (LRRK2 gene is associated with familial and sporadic PD, as exemplified by G2019S substitution. While constitutive expression of mutant LRRK2 in transgenic mice fails to induce neuron death, transient expression of the disease gene by viral delivery causes a substantial loss of dopaminergic neurons in mice. To further assess LRRK2 pathogenesis, we created inducible transgenic rats expressing human LRRK2 with G2019S substitution. Temporal overexpression of LRRK2G2019S in adult rats impaired dopamine reuptake by dopamine transporter (DAT and thus enhanced locomotor activity, the phenotypes that were not observed in transgenic rats constitutively expressing the gene throughout life time. Reduced DAT binding activity is an early sign of dopaminergic dysfunction in asymptomatic subjects carrying pathogenic mutation in LRRK2. Our transgenic rats recapitulated the initiation process of dopaminergic dysfunction caused by pathogenic mutation in LRRK2. Inducible transgenic approach uncovered phenotypes that may be obscured by developmental compensation in constitutive transgenic rats. Finding in inducible LRRK2 transgenic rats would guide developing effective strategy in transgenic studies: Inducible expression of transgene may induce greater phenotypes than constitutive gene expression, particularly in rodents with short life time.

  3. Biotechnology network promotes knowledge of transgenics

    Red de Ingenieria Genetica Aplicada al Mejoramiento de Cultivos Tropicales (Rigatrop) integrated by a group of scientists from the Universidad de Costa Rica (UCR), Universidad Nacional (UNA) and of the Instituto Tecnologico de Costa Rica (TEC) have organized two forums on the topic of transgenics. The first forum has shown successful experiences of development of transgenic crops in Latin America, as for example: the transgenic bean, project realized in Brazil and transgenic eggplant in Bangladesh. The second forum has been about transgenics and environment effected at the UCR, on the occasion of World Environment Day. Rigatrop members are working currently in two projects applying biotechnological tools to coffee

  4. Philosophical Reflection on Risks of Transgenic Technology

    Xiaolu WANG

    2012-01-01

    Abstract [Objective] The aim was to analyze risks of transgenic technology. [Method] Discussions on risks of transgenic technologies were conducted from per- spective of philosophy. [Result] Mechanistic philosophy and reductionism are causes of reflection on risks of transgenic technology. Considering transgene is an artificial choice taking place of natural choice, it is inevitable for risks of transgenic technolo- gy to be found, in addition, social system constitutes the root for out-of-control of transgenic technology, hence, mechanism risk is the primary cause of transgenic risks. [Conclusion] It is inescapable for science view to be changed from arbitrary and lopsided to reflective and comprehensive and for technology view to be changed from exterminative and genesic to protective and symbiotic.

  5. 长时程深部脑刺激外侧苍白球对转基因Huntington病大鼠认知和运动的影响%COGNITIVE AND MOTOR OUTCOME AFTER LONG-TERM GLOBUS PALLIDUS EXTERNA DEEP BRAIN STIMULATION TO TRANSGENIC HUNTINGTON'S DISEASE RAT

    曹春燕; Yasin Temel; Arjan Blokland; Veerle Visser-Vandewalle; Harry W. M. Steinbusch; 陈生弟; 刘振国

    2006-01-01

    我们研究了深部脑刺激(deep brain stimulation,DBS)对转基因Huntington病大鼠认知能力和运动功能的影响.实验结果表明:电极植入手术能改善Huntington病大鼠的认知能力,例如:在选择反应时间实验(choice reaction time task,CRTtask)中,反应准确率增加,偏倚率减少.但对不同基因型大鼠,改善程度相同.在对大鼠外侧苍白球部(GPe)进行长时间深部脑刺激后,反应准确率增加,不同基因型大鼠的增加幅度有所不同.另外,深部脑刺激后,CRT实验中的运动时间和反应时间并没有变化.但是纯合子大鼠的舞蹈样运动明显改善.本研究结果表明深部脑刺激转基因Huntington病大鼠的GPe能明显改善其认知能力和运动功能,这预示着DBS在Huntington病的治疗中将有很大的应用前景.%In this study, we treated transgenic Huntington's disease (tgHD) model rat with deep brain stimulation (DBS) and evaluated the cognitive and motor outcome. The results showed that the surgery of implanting electrode improved cognition, increased correct rate and decreased response bias in choice reaction time (CRT) task, with similar extent on various genotypes. After long-term DBS to globus pallidus externa( GPe), correct rate was enhanced. The enhancement was genotype related. Additionally, the motor time and reaction time in CRT task reflecting the movement initiation kept the same value, but the chorea-form movement of homozygous rats was rectified prominently after the treatment of DBS. The present results demonstrated that the operation of long-term DBS to globus pallidus externa can improve the cognition and motor outcome of tgHD rats, which implied DBS operation might shed light on HD patients in the future.

  6. Differential transgene expression patterns in Alzheimer mouse models revealed by novel human amyloid precursor protein-specific antibodies.

    Höfling, Corinna; Morawski, Markus; Zeitschel, Ulrike; Zanier, Elisa R; Moschke, Katrin; Serdaroglu, Alperen; Canneva, Fabio; von Hörsten, Stephan; De Simoni, Maria-Grazia; Forloni, Gianluigi; Jäger, Carsten; Kremmer, Elisabeth; Roßner, Steffen; Lichtenthaler, Stefan F; Kuhn, Peer-Hendrik

    2016-10-01

    Alzheimer's disease (AD) is histopathologically characterized by neurodegeneration, the formation of intracellular neurofibrillary tangles and extracellular Aβ deposits that derive from proteolytic processing of the amyloid precursor protein (APP). As rodents do not normally develop Aβ pathology, various transgenic animal models of AD were designed to overexpress human APP with mutations favouring its amyloidogenic processing. However, these mouse models display tremendous differences in the spatial and temporal appearance of Aβ deposits, synaptic dysfunction, neurodegeneration and the manifestation of learning deficits which may be caused by age-related and brain region-specific differences in APP transgene levels. Consequentially, a comparative temporal and regional analysis of the pathological effects of Aβ in mouse brains is difficult complicating the validation of therapeutic AD treatment strategies in different mouse models. To date, no antibodies are available that properly discriminate endogenous rodent and transgenic human APP in brains of APP-transgenic animals. Here, we developed and characterized rat monoclonal antibodies by immunohistochemistry and Western blot that detect human but not murine APP in brains of three APP-transgenic mouse and one APP-transgenic rat model. We observed remarkable differences in expression levels and brain region-specific expression of human APP among the investigated transgenic mouse lines. This may explain the differences between APP-transgenic models mentioned above. Furthermore, we provide compelling evidence that our new antibodies specifically detect endogenous human APP in immunocytochemistry, FACS and immunoprecipitation. Hence, we propose these antibodies as standard tool for monitoring expression of endogenous or transfected APP in human cells and APP expression in transgenic animals. PMID:27470171

  7. Transgenic crop-mite interactions

    Zemek, Rostislav

    France : IOBC/WPRS, 2007 - (Weintraub, P.), s. 155-160 ISBN 92-9067-200-3. [Meeting of IOBC study group "Integrated Control of Plant-feeding Mites". Jerusalem (IL), 12.03.2007-14.03.2007] R&D Projects: GA AV ČR IAA6007303 Institutional research plan: CEZ:AV0Z50070508 Keywords : GMO * transgenic plants * mites Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection

  8. Transgenic Arabidopsis Gene Expression System

    Ferl, Robert; Paul, Anna-Lisa

    2009-01-01

    The Transgenic Arabidopsis Gene Expression System (TAGES) investigation is one in a pair of investigations that use the Advanced Biological Research System (ABRS) facility. TAGES uses Arabidopsis thaliana, thale cress, with sensor promoter-reporter gene constructs that render the plants as biomonitors (an organism used to determine the quality of the surrounding environment) of their environment using real-time nondestructive Green Fluorescent Protein (GFP) imagery and traditional postflight analyses.

  9. Multicistronic lentiviral vector-mediated striatal gene transfer of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and GTP cyclohydrolase I induces sustained transgene expression, dopamine production, and functional improvement in a rat model of Parkinson's disease.

    Azzouz, Mimoun; Martin-Rendon, Enca; Barber, Robert D; Mitrophanous, Kyriacos A; Carter, Emma E; Rohll, Jonathan B; Kingsman, Susan M; Kingsman, Alan J; Mazarakis, Nicholas D

    2002-12-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra. This loss leads to complete dopamine depletion in the striatum and severe motor impairment. It has been demonstrated previously that a lentiviral vector system based on equine infectious anemia virus (EIAV) gives rise to highly efficient and sustained transduction of neurons in the rat brain. Therefore, a dopamine replacement strategy using EIAV has been investigated as a treatment in the 6-hydroxydopamine (6-OHDA) animal model of PD. A self-inactivating EIAV minimal lentiviral vector that expresses tyrosine hydroxylase (TH), aromatic amino acid dopa decarboxylase (AADC), and GTP cyclohydrolase 1 (CH1) in a single transcription unit has been generated. In cultured striatal neurons transduced with this vector, TH, AADC, and CH1 proteins can all be detected. After stereotactic delivery into the dopamine-denervated striatum of the 6-OHDA-lesioned rat, sustained expression of each enzyme and effective production of catecholamines were detected, resulting in significant reduction of apomorphine-induced motor asymmetry compared with control animals (p < 0.003). Expression of each enzyme in the striatum was observed for up to 5 months after injection. These data indicate that the delivery of three catecholaminergic synthetic enzymes by a single lentiviral vector can achieve functional improvement and thus open the potential for the use of this vector for gene therapy of late-stage PD patients. PMID:12451130

  10. Transgenic mouse offspring generated by ROSI.

    Moreira, Pedro; Pérez-Cerezales, Serafín; Laguna, Ricardo; Fernández-Gonzalez, Raúl; Sanjuanbenito, Belén Pintado; Gutiérrez-Adán, Alfonso

    2016-01-01

    The production of transgenic animals is an important tool for experimental and applied biology. Over the years, many approaches for the production of transgenic animals have been tried, including pronuclear microinjection, sperm-mediated gene transfer, transfection of male germ cells, somatic cell nuclear transfer and the use of lentiviral vectors. In the present study, we developed a new transgene delivery approach, and we report for the first time the production of transgenic animals by co-injection of DNA and round spermatid nuclei into non-fertilized mouse oocytes (ROSI). The transgene used was a construct containing the human CMV immediate early promoter and the enhanced GFP gene. With this procedure, 12% of the live offspring we obtained carried the transgene. This efficiency of transgenic production by ROSI was similar to the efficiency by pronuclear injection or intracytoplasmic injection of male gamete nuclei (ICSI). However, ICSI required fewer embryos to produce the same number of transgenic animals. The expression of Egfp mRNA and fluorescence of EGFP were found in the majority of the organs examined in 4 transgenic lines generated by ROSI. Tissue morphology and transgene expression were not distinguishable between transgenic animals produced by ROSI or pronuclear injection. Furthermore, our results are of particular interest because they indicate that the transgene incorporation mediated by intracytoplasmic injection of male gamete nuclei is not an exclusive property of mature sperm cell nuclei with compact chromatin but it can be accomplished with immature sperm cell nuclei with decondensed chromatin as well. The present study also provides alternative procedures for transgene delivery into embryos or reconstituted oocytes. PMID:26498042

  11. Transgenic animals modelling polyamine metabolism-related diseases.

    Alhonen, Leena; Uimari, Anne; Pietilä, Marko; Hyvönen, Mervi T; Pirinen, Eija; Keinänen, Tuomo A

    2009-01-01

    Cloning of genes related to polyamine metabolism has enabled the generation of genetically modified mice and rats overproducing or devoid of proteins encoded by these genes. Our first transgenic mice overexpressing ODC (ornithine decarboxylase) were generated in 1991 and, thereafter, most genes involved in polyamine metabolism have been used for overproduction of the respective proteins, either ubiquitously or in a tissue-specific fashion in transgenic animals. Phenotypic characterization of these animals has revealed a multitude of changes, many of which could not have been predicted based on the previous knowledge of the polyamine requirements and functions. Animals that overexpress the genes encoding the inducible key enzymes of biosynthesis and catabolism, ODC and SSAT (spermidine/spermine N1-acetyltransferase) respectively, appear to possess the most pleiotropic phenotypes. Mice overexpressing ODC have particularly been used as cancer research models. Transgenic mice and rats with enhanced polyamine catabolism have revealed an association of rapidly depleted polyamine pools and accelerated metabolic cycle with development of acute pancreatitis and a fatless phenotype respectively. The latter phenotype with improved glucose tolerance and insulin sensitivity is useful in uncovering the mechanisms that lead to the opposite phenotype in humans, Type 2 diabetes. Disruption of the ODC or AdoMetDC [AdoMet (S-adenosylmethionine) decarboxylase] gene is not compatible with mouse embryogenesis, whereas mice with a disrupted SSAT gene are viable and show no harmful phenotypic changes, except insulin resistance at a late age. Ultimately, the mice with genetically altered polyamine metabolism can be used to develop targeted means to treat human disease conditions that they relevantly model. PMID:20095974

  12. Integration mechanisms of transgenes and population fitness of GH transgenic fish

    2010-01-01

    It has been more than 20 years since the first batch of transgenic fish was produced. Five stable germ-line transmitted growth hormone (GH) transgenic fish lines have been generated. This paper reviews the mechanisms of integration and gene targeting of the transgene, as well as the viability, reproduction and transgenic approaches for the reproductive containment of GH-transgenic fish. Further, we propose that it should be necessary to do the following studies, in particularly, of the breeding of transgenic fish: to assess the fitness of transgenic fish in an aqueous environment with a large space and a complex structure; and to develop a controllable on-off strategy of reproduction in transgenic fish.

  13. Relevance of BAC transgene copy number in mice: transgene copy number variation across multiple transgenic lines and correlations with transgene integrity and expression

    Chandler, Kelly J.; Chandler, Ronald L.; Broeckelmann, Eva M.; HOU, YUE; Southard-Smith, E. Michelle; Mortlock, Douglas P.

    2007-01-01

    Bacterial artificial chromosomes (BACs) are excellent tools for manipulating large DNA fragments and, as a result, are increasingly utilized to engineer transgenic mice by pronuclear injection. The demand for BAC transgenic mice underscores the need for careful inspection of BAC integrity and fidelity following transgenesis, which may be crucial for interpreting transgene function. Thus, it is imperative that reliable methods for assessing these parameters are available. However, there are li...

  14. Combining M-FISH and Quantum Dot technology for fast chromosomal assignment of transgenic insertions

    Yusuf Mohammed

    2011-12-01

    Full Text Available Abstract Background Physical mapping of transgenic insertions by Fluorescence in situ Hybridization (FISH is a reliable and cost-effective technique. Chromosomal assignment is commonly achieved either by concurrent G-banding or by a multi-color FISH approach consisting of iteratively co-hybridizing the transgenic sequence of interest with one or more chromosome-specific probes at a time, until the location of the transgenic insertion is identified. Results Here we report a technical development for fast chromosomal assignment of transgenic insertions at the single cell level in mouse and rat models. This comprises a simplified 'single denaturation mixed hybridization' procedure that combines multi-color karyotyping by Multiplex FISH (M-FISH, for simultaneous and unambiguous identification of all chromosomes at once, and the use of a Quantum Dot (QD conjugate for the transgene detection. Conclusions Although the exploitation of the unique optical properties of QD nanocrystals, such as photo-stability and brightness, to improve FISH performance generally has been previously investigated, to our knowledge this is the first report of a purpose-designed molecular cytogenetic protocol in which the combined use of QDs and standard organic fluorophores is specifically tailored to assist gene transfer technology.

  15. Transcription-dependent silencing of inducible convergent transgenes in transgenic mice

    Calero-Nieto Fernando J

    2010-01-01

    Full Text Available Abstract Background Silencing of transgenes in mice is a common phenomenon typically associated with short multi-copy transgenes. We have investigated the regulation of the highly inducible human granulocyte-macrophage colony-stimulating-factor gene (Csf2 in transgenic mice. Results In the absence of any previous history of transcriptional activation, this transgene was expressed in T lineage cells at the correct inducible level in all lines of mice tested. In contrast, the transgene was silenced in a specific subset of lines in T cells that had encountered a previous episode of activation. Transgene silencing appeared to be both transcription-dependent and mediated by epigenetic mechanisms. Silencing was accompanied by loss of DNase I hypersensitive sites and inability to recruit RNA polymerase II upon stimulation. This pattern of silencing was reflected by increased methylation and decreased acetylation of histone H3 K9 in the transgene. We found that silenced lines were specifically associated with a single pair of tail-to-tail inverted repeated copies of the transgene embedded within a multi-copy array. Conclusions Our study suggests that epigenetic transgene silencing can result from convergent transcription of inverted repeats which can lead to silencing of an entire multi-copy transgene array. This mechanism may account for a significant proportion of the reported cases of transgene inactivation in mice.

  16. Transgenic Papaya: Development, Release, Impact, and Challenges

    Although the technology for developing virus-resistant transgenic plants through the use of the coat protein of a virus was unveiled twenty years ago, it is surprising to note that only a three virus-resistant plants (squash, potato, and papaya) have been commercialized in the U.S. The transgenic p...

  17. Transgenic Biofuel Feedstocks and Strategies for Biocontainment

    There are several reasons to believe that transgenic plant feedstocks will be required to realize the full economic and environmental benefits of cellulosic and other biofuels. Much of the commercialization potential for the use of transgenic plant cellulosic feedstocks may be impacted by regulatio...

  18. Expression of biologically active heterodimeric bovine follicle-stimulating hormone in milk of transgenic mice.

    Greenberg, N M; Anderson, J.W.; Hsueh, A J; Nishimori, K; Reeves, J. J.; deAvila, D M; Ward, D N; Rosen, J. M.

    1991-01-01

    Follicle-stimulating hormone (FSH; follitropin) is a pituitary glycoprotein composed of two post-translationally modified subunits, which must properly assemble to be biologically active. FSH has been difficult to purify and to obtain in quantities sufficient for detailed biochemical studies. We have targeted FSH expression to the mammary gland of transgenic mice by using cDNAs encoding the bovine alpha and FSH beta subunits and a modified rat beta-casein gene-based expression system. Lines o...

  19. Transposon-mediated chromosomal integration of transgenes in the parasitic nematode Strongyloides ratti and establishment of stable transgenic lines.

    Hongguang Shao

    Full Text Available Genetic transformation is a potential tool for analyzing gene function and thereby identifying new drug and vaccine targets in parasitic nematodes, which adversely affect more than one billion people. We have previously developed a robust system for transgenesis in Strongyloides spp. using gonadal microinjection for gene transfer. In this system, transgenes are expressed in promoter-regulated fashion in the F1 but are silenced in subsequent generations, presumably because of their location in repetitive episomal arrays. To counteract this silencing, we explored transposon-mediated chromosomal integration of transgenes in S. ratti. To this end, we constructed a donor vector encoding green fluorescent protein (GFP under the control of the Ss-act-2 promoter with flanking inverted tandem repeats specific for the piggyBac transposon. In three experiments, free-living Strongyloides ratti females were transformed with this donor vector and a helper plasmid encoding the piggyBac transposase. A mean of 7.9% of F1 larvae were GFP-positive. We inoculated rats with GFP-positive F1 infective larvae, and 0.5% of 6014 F2 individuals resulting from this host passage were GFP-positive. We cultured GFP-positive F2 individuals to produce GFP-positive F3 L3i for additional rounds of host and culture passage. Mean GFP expression frequencies in subsequent generations were 15.6% in the F3, 99.0% in the F4, 82.4% in the F5 and 98.7% in the F6. The resulting transgenic lines now have virtually uniform GFP expression among all progeny after at least 10 generations of passage. Chromosomal integration of the reporter transgenes was confirmed by Southern blotting and splinkerette PCR, which revealed the transgene flanked by S. ratti genomic sequences corresponding to five discrete integration sites. BLAST searches of flanking sequences against the S. ratti genome revealed integrations in five contigs. This result provides the basis for two powerful functional genomic tools

  20. Generation of transgenic Hydra by embryo microinjection.

    Juliano, Celina E; Lin, Haifan; Steele, Robert E

    2014-01-01

    As a member of the phylum Cnidaria, the sister group to all bilaterians, Hydra can shed light on fundamental biological processes shared among multicellular animals. Hydra is used as a model for the study of regeneration, pattern formation, and stem cells. However, research efforts have been hampered by lack of a reliable method for gene perturbations to study molecular function. The development of transgenic methods has revitalized the study of Hydra biology(1). Transgenic Hydra allow for the tracking of live cells, sorting to yield pure cell populations for biochemical analysis, manipulation of gene function by knockdown and over-expression, and analysis of promoter function. Plasmid DNA injected into early stage embryos randomly integrates into the genome early in development. This results in hatchlings that express transgenes in patches of tissue in one or more of the three lineages (ectodermal epithelial, endodermal epithelial, or interstitial). The success rate of obtaining a hatchling with transgenic tissue is between 10% and 20%. Asexual propagation of the transgenic hatchling is used to establish a uniformly transgenic line in a particular lineage. Generating transgenic Hydra is surprisingly simple and robust, and here we describe a protocol that can be easily implemented at low cost. PMID:25285460

  1. Glyphostate-drift but not herbivory alters the rate of transgene flow from single and stacked trait transgenic canola (Brassica napus L.) to non-transgenic B. napus and B. rapa

    While transgenic plants can offer agricultural benefits, the escape of transgenes out of crop fields is a major environmental concern. Escape of transgenic herbicide resistance has occurred between transgenic Brassica napus (canola) and weedy species in numerous locations. In t...

  2. Transgenic fish: present status and future directions.

    Hew, C L

    1989-06-01

    Successful production of transgenic fish by gene transfer technology is a very important breakthrough in the techniques of genetic manipulation in animals. This will have an impact of an unprecedented scale in fish biology, aquaculture and mariculture. This is a summary of the workshop on the Transgenic Fish presented at this Symposium. The Workshop discussed the current knowledge, experimental difficulties and related topics of the transgenic fish. It recommended further research on better gene constructs, methods development, safety containment and the closer collaboration of researchers of different disciplines. PMID:24221801

  3. Expression of multiple proteins in transgenic plants

    Vierstra, Richard D.; Walker, Joseph M.

    2002-01-01

    A method is disclosed for the production of multiple proteins in transgenic plants. A DNA construct for introduction into plants includes a provision to express a fusion protein of two proteins of interest joined by a linking domain including plant ubiquitin. When the fusion protein is produced in the cells of a transgenic plant transformed with the DNA construction, native enzymes present in plant cells cleave the fusion protein to release both proteins of interest into the cells of the transgenic plant. Since the proteins are produced from the same fusion protein, the initial quantities of the proteins in the cells of the plant are approximately equal.

  4. Persistence, localization, and external control of transgene expression after single injection of adeno-associated virus into injured joints.

    Lee, Hannah H; O'Malley, Michael J; Friel, Nicole A; Payne, Karin A; Qiao, Chunping; Xiao, Xiao; Chu, Constance R

    2013-04-01

    A single intra-articular injection of adeno-associated virus (AAV) results in stable and controllable transgene expression in normal rat knees. Because undamaged joints are unlikely to require treatment, the study of AAV delivery in joint injury models is crucial to potential therapeutic applications. This study tests the hypotheses that persistent and controllable AAV-transgene expression are (1) highly localized to the cartilage when AAV is injected postinjury and (2) localized to the intra-articular soft tissues when AAV is injected preinjury. Two AAV injection time points, postinjury and preinjury, were investigated in osteochondral defect and anterior cruciate ligament transection models of joint injury. Rats injected with AAV tetracycline response element (TRE)-luciferase received oral doxycycline for 7 days. Luciferase expression was evaluated longitudinally for 6 months. Transgene expression was persistent and controllable with oral doxycycline for 6 months in all groups. However, the location of transgene expression was different: postinjury AAV-injected knees had luciferase expression highly localized to the cartilage, while preinjury AAV-injected knees had more widespread signal from intra-articular soft tissues. The differential transgene localization between preinjury and postinjury injection can be used to optimize treatment strategies. Highly localized postinjury injection appears advantageous for treatments targeting repair cells. The more generalized and controllable reservoir of transgene expression following AAV injection before anterior cruciate ligament transection (ACLT) suggests an intriguing concept for prophylactic delivery of joint protective factors to individuals at high risk for early osteoarthritis (OA). Successful external control of intra-articular transgene expression provides an added margin of safety for these potential clinical applications. PMID:23496155

  5. Comparison of the antibody responses to the 77 Klebsiella capsular types in ankylosing spondylitis and various rheumatic diseases.

    Sahly, H; Kekow, J; Podschun, R.; Schaff, M; Gross, W. L.; Ullmann, U

    1994-01-01

    The production of antibodies to Klebsiella capsular polysaccharides was measured in sera from either HLA-B27-positive (HLA-B27+) or HLA-B27-negative (HLA-B27-) patients with classical ankylosing spondylitis (n = 54). These sera were compared with sera from patients with various rheumatic diseases (n = 82) and HLA-B27+ or HLA-B27- healthy individuals (n = 85). All sera were analyzed by means of an enzyme-linked immunosorbent assay specific to each of the 77 Klebsiella serotypes. The sera from ...

  6. HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom.

    M A Brown; Pile, K D; Kennedy, L G; Calin, A.; Darke, C; Bell, J.; Wordsworth, B P; Cornélis, F

    1996-01-01

    OBJECTIVE: To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. METHODS: HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically mat...

  7. Transgenic mice overexpressing insulin-like growth factor-II in β cells develop type 2 diabetes

    Devedjian, Jean-Christophe; George, Monica; Casellas, Alba; Pujol, Anna; Visa, Joana; Pelegrín, Mireia; Gros, Laurent; Bosch, Fatima

    2000-01-01

    During embryonic development, insulin-like growth factor-II (IGF-II) participates in the regulation of islet growth and differentiation. We generated transgenic mice (C57BL6/SJL) expressing IGF-II in β cells under control of the rat Insulin I promoter in order to study the role of islet hyperplasia and hyperinsulinemia in the development of type 2 diabetes. In contrast to islets from control mice, islets from transgenic mice displayed high levels of IGF-II mRNA and protein. Pancreases from tr...

  8. Stable Skin-specific Overexpression of Human CTLA4-Ig in Transgenic Mice through Seven Generations

    Yong WANG; Yong NI; Hong WEI; Feng-Chao WANG; Liang-Peng GE; Xiang GAO

    2006-01-01

    Skin graft rejection is a typical cellular immune response, mainly mediated by T cells. Cytotoxic T lymphocyte associated antigen 4-immunoglobin (CTLA4-Ig) extends graft survival by blocking the T cell co-stimulation pathway and inhibiting T cell activation. To investigate the efficacy of CTLA4-Ig in prolonging skin graft survival, human CTLA4-Ig (hCTLA4-Ig) was engineered to overexpress in mouse skin by transgenesis using the K14 promoter. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay indicated that the expression of CTLA4-Ig remained skin-specific and relatively constant compared to the internal control protein, AKT, through seven generations. The presence and concentration of the hCTLA4-Ig protein in transgenic mouse sera was determined by enzyme-linked immunosorbent assay (ELISA), and the results indicated that the serum CTLA4-Ig concentration also remained constant through generations. Survival of transgenic mouse skins grafted onto rat wounds was remarkably prolonged compared to that of wild-type skins from the same mouse strain, and remained comparable among all seven generations. This suggested that the bioactive hCTLA4-Ig protein was stably expressed in transgenical mice through at least seven generations, which was consistent with the stable skin-specific CTLA4-Ig expression.The results demonstrated that the transgenic expression of hCTLA4-Ig in skin driven by the K14 promoter remained constant through generations, and a transgenic line can be established to provide transgenic skin with extended survival reproducibly.

  9. Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen

    Mössner Joachim

    2006-10-01

    Full Text Available Abstract Background The R122H mutation of the cationic trypsinogen was found in patients with hereditary pancreatitis. A transgenic animal carrying this mutation could be useful as a genetic model system of pancreatitis. Methods Mice transgenic for the human R122H cationic trypsinogen were generated using the -205 fragment of the rat elastase promoter. The presence of the transgene was assayed in the DNA, in pancreatic mRNA and in zymogen granule lysates. Serum levels of amylase, lipase and cytokines (MCP-1, IL-6 were monitored and the histological appearance of the tissue was investigated. Pancreatitis was induced by 7 hourly injections of 50 μg/kg cerulein. The procedure was repeated twice weekly for 10 consecutive weeks. The animals were sacrificed 24 (n = 8 and 48 hours (n = 8 after the first injection and at the end of the whole treatment (n = 7. Results The transgene was detected at the genomic level and in pancreatic mRNA. The corresponding protein was found in low amounts in zymogen granule lysates. R122H mice showed elevated pancreatic lipase, but there was no spontaneous development of pancreatitis within 18 months. After induction of pancreatitis, levels of lipase (after 24 hours and amylase (after 48 hours were higher in R122H mice compared to controls. Repeated treatment with cerulein resulted in a slightly more severe pancreatitis in R122H animals. Amylase, lipase, and the cytokine levels were similar to controls. Conclusion The R122H transgenic mouse failed to develop a spontaneous pancreatitis but a repeatedly provoked cerulein-induced pancreatitis led to a slightly more severe pancreatitis. The rather small difference in comparison to controls could be due to the low expression of the transgene in the mouse pancreas.

  10. Transgenic plants with enhanced growth characteristics

    Unkefer, Pat J.; Anderson, Penelope S.; Knight, Thomas J.

    2016-09-06

    The invention relates to transgenic plants exhibiting dramatically enhanced growth rates, greater seed and fruit/pod yields, earlier and more productive flowering, more efficient nitrogen utilization, increased tolerance to high salt conditions, and increased biomass yields. In one embodiment, transgenic plants engineered to over-express both glutamine phenylpyruvate transaminase (GPT) and glutamine synthetase (GS) are provided. The GPT+GS double-transgenic plants of the invention consistently exhibit enhanced growth characteristics, with T0 generation lines showing an increase in biomass over wild type counterparts of between 50% and 300%. Generations that result from sexual crosses and/or selfing typically perform even better, with some of the double-transgenic plants achieving an astounding four-fold biomass increase over wild type plants.

  11. [Review of transgenic crop breeding in China].

    Huang, Dafang

    2015-06-01

    The development history and fundamental experience of transgenic crops (Genetically modified crops) breeding in China for near 30 years were reviewed. It was illustrated that a scientific research, development and industrialization system of transgenic crops including gene discovery, transformation, variety breeding, commercialization, application and biosafety assessment has been initially established which was few in number in the world. The research innovative capacity of transgenic cotton, rice and corn has been lifted. The research features as well as relative advantages have been initially formed. The problems and challenges of transgenic crop development were discussed. In addition, three suggestions of promoting commercialization, speeding up implementation of the Major National Project of GM Crops, and enhancing science communication were made. PMID:26672365

  12. Accumulation of nickel in transgenic tobacco

    Sidik, Nik Marzuki; Othman, Noor Farhan

    2013-11-01

    The accumulation of heavy metal Ni in the roots and leaves of four T1 transgenic lines of tobacco (T(1)20E, T(1)24C, T(1)18B1 and T(1)20B) expressing eiMT1 from E.indica was assessed. The aim of the study was to investigate the level of Ni accumulation in the leaves and roots of each transgenic lines and to evaluate the eligibility of the plants to be classified as a phytoremediation agent. All of the transgenic lines showed different ability in accumulating different metals and has translocation factor (TF) less than 1 (TFtransgenic lines, transgenic line T(1)24C showed the highest accumulation of Ni (251.9 ± 0.014 mg/kg) and the lowest TF value (TFT(1)24C=0.0875) at 60 ppm Ni.

  13. Comparison of nutritional value of transgenic peanut expressing bar and rcg3 genes with non-transgenic counterparts

    The transgenic peanut plants expressing bar and rcg3 genes were subjected to assessment of any change in nutritional value of the crop at various locations. The protein and fat contents of transgenic lines were compared with the non-transgenic parent varieties. Protein content in the transgenic lines was higher as compared to that in non-transgenic counterparts and differences among locations for fat and protein content were significant. No differences among fatty acids were recorded for genes, events and locations. Irrespective of small differences, all the values were in range described for this crop and transgenic lines appeared to be substantially equivalent to non-transgenic parent varieties. (author)

  14. Eosinophilia in transgenic mice expressing interleukin 5

    1990-01-01

    Experiments in vitro suggest that although interleukin 5 (IL-5) stimulates the late stages of eosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the IL-5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two of which w...

  15. TRANSGENIC FISH MODEL IN ENVIRONMENTAL TOXICOLOGY

    Madhuri Sharma

    2012-05-01

    Full Text Available A number of experiments and the use of drugs have been performed in fish. The fish may be used as model organism in various biological experiments, including environmental toxicology. Aquatic animals are being engineered to increase aquaculture production, for medical and industrial research, and for ornamental reasons. Fish have been found to play an important role in assessing potential risks associated with exposure to toxic substances in aquatic environment. Hence, it has been thought that the development of transgenic fish can enhance the use of fish in environmental toxicology. India has developed experimental transgenics of rohu fish, zebra fish, cat fish and singhi fish. Genes, promoters and vectors of indigenous origin are now available for only two species namely rohu and singhi for engineering growth. Development of fish model carrying identical transgenes to those found in rodents is beneficial and has shown that several aspects of in vivo mutagenesis are similar between the two classes of vertebrates. Fish shows the frequencies of spontaneous mutations similar to rodents and respond to mutagen exposure consistent with known mutagenic mechanisms. The feasibility of in vivo mutation analysis using transgenic fish has been demonstrated and the potential value of transgenic fish as a comparative animal model has been illustrated. Therefore, the transgenic fish can give the significant contribution to study the environmental toxicity in animals as a whole.

  16. Hypertensive retinopathy in a transgenic angiotensin-based model.

    Reichhart, Nadine; Haase, Nadine; Crespo-Garcia, Sergio; Skosyrski, Sergej; Herrspiegel, Christina; Kociok, Norbert; Fuchshofer, Rudolf; Dillinger, Andrea; Poglitsch, Marco; Müller, Dominik N; Joussen, Antonia M; Luft, Friedrich C; Dechend, Ralf; Strauß, Olaf

    2016-07-01

    Severe hypertension destroys eyesight. The RAS (renin-angiotensin system) may contribute to this. This study relied on an established angiotensin, AngII (angiotensin II)-elevated dTGR (double-transgenic rat) model and same-background SD (Sprague-Dawley) rat controls. In dTGRs, plasma levels of AngII were increased. We determined the general retinal phenotype and observed degeneration of ganglion cells that we defined as vascular degeneration. We also inspected relevant gene expression and lastly observed alterations in the outer blood-retinal barrier. We found that both scotopic a-wave and b-wave as well as oscillatory potential amplitude were significantly decreased in dTGRs, compared with SD rat controls. However, the b/a-wave ratio remained unchanged. Fluorescence angiography of the peripheral retina indicated that exudates, or fluorescein leakage, from peripheral vessels were increased in dTGRs compared with controls. Immunohistological analysis of blood vessels in retina whole-mount preparations showed structural alterations in the retina of dTGRs. We then determined the general retinal phenotype. We observed the degeneration of ganglion cells, defined vascular degenerations and finally found differential expression of RAS-related genes and angiogenic genes. We found the expression of both human angiotensinogen and human renin in the hypertensive retina. Although the renin gene expression was not altered, the AngII levels in the retina were increased 4-fold in the dTGR retina compared with that in SD rats, a finding with mechanistic implications. We suggest that alterations in the outer blood-retinal barrier could foster an area of visual-related research based on our findings. Finally, we introduce the dTGR model of retinal disease. PMID:27026533

  17. Possible ecological risks of transgenic organism release when transgenes affect mating success: Sexual selection and the Trojan gene hypothesis

    Muir, William M.; Howard, Richard D.

    1999-01-01

    Widespread interest in producing transgenic organisms is balanced by concern over ecological hazards, such as species extinction if such organisms were to be released into nature. An ecological risk associated with the introduction of a transgenic organism is that the transgene, though rare, can spread in a natural population. An increase in transgene frequency is often assumed to be unlikely because transgenic organisms typically have some viability disadvantage. Reduced viability is assumed...

  18. Transgenic technologies to induce sterility

    Wimmer Ernst A

    2009-11-01

    Full Text Available Abstract The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes.

  19. Selenoprotein-Transgenic Chlamydomonas reinhardtii

    Jiazuan Ni

    2013-02-01

    Full Text Available Selenium (Se deficiency is associated with the occurrence of many diseases. However, excessive Se supplementation, especially with inorganic Se, can result in toxicity. Selenoproteins are the major forms of Se in vivo to exert its biological function. Expression of those selenoproteins, especially with the application of a newly developed system, is thus very important for studying the mechanism of Se in nutrition. The use of Chlamydomonas reinhardtii (C. reinhardtii as a biological vector to express an heterogeneous protein is still at the initial stages of development. In order to investigate the possibility of using this system to express selenoproteins, human 15-KDa selenoprotein (Sep15, a small but widely distributed selenoprotein in mammals, was chosen for the expression platform test. Apart from the wild-type human Sep15 gene fragment, two Sep15 recombinants were constructed containing Sep15 open reading frame (ORF and the selenocysteine insertion sequence (SECIS element from either human Sep15 or C. reinhardtii selenoprotein W1, a highly expressed selenoprotein in this alga. Those Sep15-containing plasmids were transformed into C. reinhardtii CC-849 cells. Results showed that Sep15 fragments were successfully inserted into the nuclear genome and expressed Sep15 protein in the cells. The transgenic and wild-type algae demonstrated similar growth curves in low Se culture medium. To our knowledge, this is the first report on expressing human selenoprotein in green alga.

  20. Mutagenicity of comfrey (Symphytum Officinale) in rat liver.

    Mei, N; Guo, L; Fu, P P; Heflich, R H; Chen, T

    2005-03-14

    Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant. PMID:15726100

  1. Mutagenicity of comfrey (Symphytum Officinale) in rat liver

    MEI, N.; Guo, L.; Fu, P P; Heflich, R H; Chen, T.

    2005-01-01

    Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant.

  2. The rat as an animal model of Alzheimer's disease

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt

    2009-01-01

    As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer's disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind that...... of mice. In recent years, the rat has been making a comeback as an Alzheimer's disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to the existing mouse models. This review summarizes the contributions and current status of the rat as an...... animal model of Alzheimer's disease....

  3. The transgenic animal platform for biopharmaceutical production.

    Bertolini, L R; Meade, H; Lazzarotto, C R; Martins, L T; Tavares, K C; Bertolini, M; Murray, J D

    2016-06-01

    The recombinant production of therapeutic proteins for human diseases is currently the largest source of innovation in the pharmaceutical industry. The market growth has been the driving force on efforts for the development of new therapeutic proteins, in which transgenesis emerges as key component. The use of the transgenic animal platform offers attractive possibilities, residing on the low production costs allied to high productivity and quality of the recombinant proteins. Although many strategies have evolved over the past decades for the generation of transgenic founders, transgenesis in livestock animals generally faces some challenges, mainly due to random transgene integration and control over transgene copy number. But new developments in gene editing with CRISPR/Cas system promises to revolutionize the field for its simplicity and high efficiency. In addition, for the final approval of any given recombinant protein for animal or human use, the production and characterization of bioreactor founders and expression patterns and functionality of the proteins are technical part of the process, which also requires regulatory and administrative decisions, with a large emphasis on biosafety. The approval of two mammary gland-derived recombinant proteins for commercial and clinical use has boosted the interest for more efficient, safer and economic ways to generate transgenic founders to meet the increasing demand for biomedical proteins worldwide. PMID:26820414

  4. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats

    Schrøder, Malene; Poulsen, Morten; Wilcks, Andrea;

    2007-01-01

    An animal model for safety assessment of genetically modified foods was tested as part of the SAFOTEST project. In a 90-day feeding study on Wistar rats, the transgenic KMD1 rice expressing Cry1Ab protein was compared to its non-transgenic parental wild type, Xiushui 11. The KMD1 rice contained 1...

  5. Screening for transgenic Japanese quail offspring.

    Poynter, Greg; Huss, David; Lansford, Rusty

    2009-01-01

    After mosaic founder breeding pairs of Japanese quail start to produce fertile eggs, the hatchlings must be screened for germ-line transmission to the subsequent G1 generation. This article describes how to isolate hatchling genomic DNA from the chorioallantoic membrane (CAM), which remains inside the egg after hatching. Collecting genomic DNA from the CAM decreases the hatchling's stress during handling and eliminates the need for a blood draw. By following this protocol, the CAM of a single egg will provide 50 microg or more of high-quality genomic DNA. The article also describes how to screen the genomic DNA samples for the transgene by the polymerase chain reaction (PCR). PCR genotyping should be used for screening hatchlings with a nonfluorescent transgene or with a fluorescently labeled transgene that does not lend itself well to phenotypic screening. PMID:20147014

  6. Histocompatibility antigen test

    ... more common in certain autoimmune diseases . For example, HLA-B27 antigen is found in many people (but not ... More Ankylosing spondylitis Autoimmune disorders Bone marrow transplant HLA-B27 antigen Kidney transplant Reactive arthritis Update Date 2/ ...

  7. Genetics Home Reference: ankylosing spondylitis

    ... A variation of the HLA-B gene called HLA-B27 increases the risk of developing ankylosing spondylitis . Although many people with ankylosing spondylitis have the HLA-B27 variation, most people with this version of the ...

  8. Influence of DNA methylation on transgene expression

    2001-01-01

    DNA methylation plays an important role in gene expression in eukaryote. But DNA methylation of transgene usually leads to target gene silencing in plant genetic engineering. In this research, reporter gene b-glu- curonidase (GUS) gene (uidA) was introduced into tobaccos via Agrobacterium-mediated transformation method, and the foreign uidA gene became inactive in some transgenic tobaccos. No mRNA of uidA was detected in these plants by Northern blotting analysis, and DNA methylation of promoter region was found. The results indicated that gene silencing might be caused by DNA methylation of promoter.

  9. Generation of BAC transgenic epithelial organoids.

    Gerald Schwank

    Full Text Available Under previously developed culture conditions, mouse and human intestinal epithelia can be cultured and expanded over long periods. These so-called organoids recapitulate the three-dimensional architecture of the gut epithelium, and consist of all major intestinal cell types. One key advantage of these ex vivo cultures is their accessibility to live imaging. So far the establishment of transgenic fluorescent reporter organoids has required the generation of transgenic mice, a laborious and time-consuming process, which cannot be extended to human cultures. Here we present a transfection protocol that enables the generation of recombinant mouse and human reporter organoids using BAC (bacterial artificial chromosome technology.

  10. Transgenic cultures: from the economic viewpoint

    Mauricio Mosquera

    2011-12-01

    Full Text Available The introduction of transgenic seeds for agricultural purposes poses modification to their production, due to the potential for reaching desired characteristics such as greater yield, this being fundamental in an economic environment characterised by open market conditions. However, acceptance of products resulting from genetic engineering is far from becoming a simple process; discussion relating to the predominance of private sector interests, the monopoly of knowledge and the safety of such seeds/food is currently in the spotlight. This article presents the main points of debate regarding adoption of transgenic cultures, contributing to discussion about this topic for Colombia.

  11. Lectin cDNA and transgenic plants derived therefrom

    Raikhel, Natasha V.

    2000-10-03

    Transgenic plants containing cDNA encoding Gramineae lectin are described. The plants preferably contain cDNA coding for barley lectin and store the lectin in the leaves. The transgenic plants, particularly the leaves exhibit insecticidal and fungicidal properties.

  12. Production of homozygous transgenic rainbow trout with enhanced disease resistance.

    Chiou, Pinwen Peter; Chen, Maria J; Lin, Chun-Mean; Khoo, Jenny; Larson, Jon; Holt, Rich; Leong, Jo-Ann; Thorgarrd, Gary; Chen, Thomas T

    2014-06-01

    Previous studies conducted in our laboratory showed that transgenic medaka expressing cecropin B transgenes exhibited resistant characteristic to fish bacterial pathogens, Pseudomonas fluorescens and Vibrio anguillarum. To confirm whether antimicrobial peptide gene will also exhibit anti-bacterial and anti-viral characteristics in aquaculture important fish species, we produced transgenic rainbow trout expressing cecropin P1 or a synthetic cecropin B analog, CF-17, transgene by sperm-mediated gene transfer method. About 30 % of fish recovered from electroporation were shown to carry the transgene as determined by polymerase chain reaction (PCR) amplification assay. Positive P₁ transgenic fish were crossed to non-transgenic fish to establish F₁ transgenic founder families, and subsequently generating F₂, and F₃ progeny. Expression of cecropin P1 and CF-17 transgenes was detected in transgenic fish by reverse transcription (RT)-PCR analysis. The distribution of body sizes among F₁ transgenic fish were not significantly different from those of non-transgenic fish. Results of challenge studies revealed that many families of F₂ and F₃ transgenic fish exhibited resistance to infection by Aeromonas salmonicida and infectious hematopoietic necrosis virus (IHNV). All-male homozygous cecropin P1 transgenic families were produced by androgenesis from sperm of F₃ heterozygous transgenic fish in one generation. The resistant characteristic to A. salmonicida was confirmed in progeny derived from the outcross of all-male fish to non-transgenic females. Results of our current studies confirmed the possibility of producing disease-resistant homozygous rainbow trout strains by transgenesis of cecropin P1 or CF-17 gene and followed by androgenesis. PMID:24085608

  13. Dataset for the role of sustained attention in memory formation of transgenic mice for Alzheimer׳s disease

    Natalia Mendes Schöwe

    2016-03-01

    Full Text Available Weekly submission of rats to active avoidance apparatus can be considered a neurostimulation strategy, once it can improve memory and can increase the density of receptors from different neurotransmitter systems in brain areas related to memory. These benefits were observed in rats chronically infused with amyloid-β peptide. In the present work it is presented that the same benefit for memory was observed in five months old transgenic mice for Alzheimer’s disease (TG-PDGFB-APPSw,Ind. However, at this age, no change in density of nicotinic receptors was observed.

  14. Comparative metallomics of transgenic and non-transgenic soybeans using HPLC-ICP-MS

    Complete text of publication follows. In the last years, many soybean varieties have been developed, and due to these modifications, the proteins composition and profile can be affected, causing changes in the species proteome (S. Natarajan et al., Anal. Biochem., 342 (2005), 214-220.). With the proteome modifications, the metallome of this specie, defined as the total content of metals and metalloids in a cell or tissue (J. Spuznar, Analyst, 130 (2005), 442-465.), can also be affected (A. Sussulini et al., J. Anal. At. Spectrom., 22 (2007), 1501-1506.). So, the aim of this work is to amplify the information about the transgenic and non-transgenic soybeans metallome, and doing that we expect to find biomarkers that can differentiate the transgenic and non-transgenic soybeans physiologically. For that purpose a SEC column (GE Healthcare, model Superdex 200) was employed for the separation of the proteins, which were extracted using the mobile phase of the chromatographic system (90 mmol.L-1 phosphate buffer - pH 7.2). After the chromatographic separation, the eluate was passed through a DAD Series 200 detector (PerkinElmer), the fractions were collected and latter introduced into the ICP-MS (PerkinElmer, model ELANDRC-e) for the element-selective detection. The calibration of the column using purified proteins of known molecular weight allowed the calculation of the approximate masses of the eight fractions (1800-800 kDa; 800-420 kDa; 420-120 kDa; 100-23 kDa; 23-7 kDa; 7-2 kDa; 2-0.4 kDa and 0.4-0.2 kDa, respectively) identified in the transgenic and non-transgenic soybeans after 95 min of separation using a flow rate of 0.25 mL.min-1. A wide range of elements could be identified in all the fractions, including: Cu, Zn, Mn, Mg, Ni, Cr, Hg, Fe and Pb. Differences in the detectability of elements in the transgenic and non-transgenic soybeans were found, specially for Hg where the counts were two times higher in the transgenic soybean. Elements were found in the two

  15. Biological containment strategies for transgenic crops

    Maagd, de R.A.; Boutilier, K.A.

    2013-01-01

    Biological containment is the prevention or reduction in the spread of transgenes by modifying plant growth or development, most commonly through modification of reproductive characteristics. This review provides a summary of the current strategies for biological containment, including the use of bo

  16. A transgenic mouse model for trilateral retinoblastoma

    O'Brien, J.M.; Marcus, D.M.; Bernards, R.A.; Carpenter, J.L.; Windle, J.J.; Mellon, P.; Albert, D.M.

    1990-01-01

    We present a murine model of trilateral retinoblastoma. Ocular retinoblastoma and central nervous system tumors are observed in a line of mice formed by the transgenic expression of SV40 T-antigen. An oncogenic protein known to bind to the retinoblastoma gene product (p105-Rb) is specifically expres

  17. Metal resistance sequences and transgenic plants

    Meagher, Richard Brian; Summers, Anne O.; Rugh, Clayton L.

    1999-10-12

    The present invention provides nucleic acid sequences encoding a metal ion resistance protein, which are expressible in plant cells. The metal resistance protein provides for the enzymatic reduction of metal ions including but not limited to divalent Cu, divalent mercury, trivalent gold, divalent cadmium, lead ions and monovalent silver ions. Transgenic plants which express these coding sequences exhibit increased resistance to metal ions in the environment as compared with plants which have not been so genetically modified. Transgenic plants with improved resistance to organometals including alkylmercury compounds, among others, are provided by the further inclusion of plant-expressible organometal lyase coding sequences, as specifically exemplified by the plant-expressible merB coding sequence. Furthermore, these transgenic plants which have been genetically modified to express the metal resistance coding sequences of the present invention can participate in the bioremediation of metal contamination via the enzymatic reduction of metal ions. Transgenic plants resistant to organometals can further mediate remediation of organic metal compounds, for example, alkylmetal compounds including but not limited to methyl mercury, methyl lead compounds, methyl cadmium and methyl arsenic compounds, in the environment by causing the freeing of mercuric or other metal ions and the reduction of the ionic mercury or other metal ions to the less toxic elemental mercury or other metals.

  18. Transgenic plants with increased calcium stores

    Wyatt, Sarah (Inventor); Tsou, Pei-Lan (Inventor); Robertson, Dominique (Inventor); Boss, Wendy (Inventor)

    2004-01-01

    The present invention provides transgenic plants over-expressing a transgene encoding a calcium-binding protein or peptide (CaBP). Preferably, the CaBP is a calcium storage protein and over-expression thereof does not have undue adverse effects on calcium homeostasis or biochemical pathways that are regulated by calcium. In preferred embodiments, the CaBP is calreticulin (CRT) or calsequestrin. In more preferred embodiments, the CaBP is the C-domain of CRT, a fragment of the C-domain, or multimers of the foregoing. In other preferred embodiments, the CaBP is localized to the endoplasmic reticulum by operatively associating the transgene encoding the CaBP with an endoplasmic reticulum localization peptide. Alternatively, the CaBP is targeted to any other sub-cellular compartment that permits the calcium to be stored in a form that is biologically available to the plant. Also provided are methods of producing plants with desirable phenotypic traits by transformation of the plant with a transgene encoding a CaBP. Such phenotypic traits include increased calcium storage, enhanced resistance to calcium-limiting conditions, enhanced growth and viability, increased disease and stress resistance, enhanced flower and fruit production, reduced senescence, and a decreased need for fertilizer production. Further provided are plants with enhanced nutritional value as human food or animal feed.

  19. Effect of transgene number of spontaneous and radiation-induced micronuclei in lacl transgenic mice

    Lacl transgenic mice are widely used for the measurement of mutations in specific target issues. The lacl transgene is present in mice as 40 tandem repeats; this sequence is homozygous (contained in both copies of chromosome 5) in C57Bl/6 mice, and is hemizygous in B6C3F1 mice. Previous reports have indicated that tandem repeats can produce chromosome instability, fragile sites, and other effects. To determine whether the presence of the transgene effects micronucleus induction we compared the response of nontransgenic (NTR) to hemizygous (HEMI) transgenic B6C3F1 mice and to hemizygous and homozygous (HOMO) transgenic C57Bl/6 mice. Five mice/group were irradiated with 500 cGy from a 137Cs source. Bone marrow was harvested 24 hr after treatment and 2000 polychromatic erythrocytes (PCE) were analyzed per animal. The presence or absence of the lacl transgene had no effect in unirradiated mice on the percent of micronucleated PCE (MN) or on the ratio of PCE to total red blood cells for either strain: B6C3F1 mice had MN frequencies of 0.26% and 0.20% for NTR and HEMI mice, respectively; C57Bl/6 mice had MN frequencies of 0.34%, 0.32%, and 0.38% for NTR, HEMI, and HOMO mice, respectively. Radiation-induced micronucleus frequencies were significantly higher in HEMI lacl B6C3F1 mice (2.85%) than in NTR litter mates (1.59%); the converse was true in C57Bl/6 mice: NTR were 2.45%, HEMI were 1.25%, HOMO were 1.65%. These data suggest that the lacl transgene does not cause chromosome instability as measured by spontaneous micronucleus levels. However, the response of these transgenic mice to a variety of clastogenic agents needs to be investigated before they are integrated into standard in vivo assays for chromosome damage

  20. Characterization of transgene integration pattern in F4 hGH-transgenic common carp (Cyprinus carpio L.)

    Bo WU; Yong Hua SUN; Yan Wu WANG; Ya Ping WANG; Zuo Yan ZHU

    2005-01-01

    The integration pattern and adjacent host sequences of the inserted pMThGH-transgene in the F4 hGH-transgenic common carp were extensively studied. Here we show that each F4 transgenic fish contained about 200 copies of the pMThGH-transgene and the transgenes were integrated into the host genome generally with concatemers in a head-totail arrangement at 4-5 insertion sites. By using a method of plasmid rescue, four hundred copies of transgenes from two individuals of F4 transgenic fish, A and B, were recovered and clarified into 6 classes. All classes of recovered transgenes contained either complete or partial pMThGH sequences. The class Ⅰ, which comprised 83% and 84.5% respectively of the recovered transgene copies from fish A and B, had maintained the original configuration, indicating that most transgenes were faithfully inherited during the four generations of reproduction. The other five classes were different from the original configuration in both molecular weight and restriction map, indicating that a few transgenes had undergone mutation, rearrangement or deletion during integration and germline transmission. In the five types of aberrant transgenes, three flanking sequences of the host genome were analyzed. These sequences were common carp β-actin gene, common carp DNA sequences homologous to mouse phosphoglycerate kinase-1 and human epidermal keratin 14, respectively.

  1. Split-Cre complementation restores combination activity on transgene excision in hair roots of transgenic tobacco.

    Mengling Wen

    Full Text Available The Cre/loxP system is increasingly exploited for genetic manipulation of DNA in vitro and in vivo. It was previously reported that inactive ''split-Cre'' fragments could restore Cre activity in transgenic mice when overlapping co-expression was controlled by two different promoters. In this study, we analyzed recombination activities of split-Cre proteins, and found that no recombinase activity was detected in the in vitro recombination reaction in which only the N-terminal domain (NCre of split-Cre protein was expressed, whereas recombination activity was obtained when the C-terminal (CCre or both NCre and CCre fragments were supplied. We have also determined the recombination efficiency of split-Cre proteins which were co-expressed in hair roots of transgenic tobacco. No Cre recombination event was observed in hair roots of transgenic tobacco when the NCre or CCre genes were expressed alone. In contrast, an efficient recombination event was found in transgenic hairy roots co-expressing both inactive split-Cre genes. Moreover, the restored recombination efficiency of split-Cre proteins fused with the nuclear localization sequence (NLS was higher than that of intact Cre in transgenic lines. Thus, DNA recombination mediated by split-Cre proteins provides an alternative method for spatial and temporal regulation of gene expression in transgenic plants.

  2. Can transgenic maize affect soil microbial communities?

    Mulder, Christian; Wouterse, Marja; Raubuch, Markus; Roelofs, Willem; Rutgers, Michiel

    2006-09-29

    The aim of the experiment was to determine if temporal variations of belowground activity reflect the influence of the Cry1Ab protein from transgenic maize on soil bacteria and, hence, on a regulatory change of the microbial community (ability to metabolize sources belonging to different chemical guilds) and/or a change in numerical abundance of their cells. Litter placement is known for its strong influence on the soil decomposer communities. The effects of the addition of crop residues on respiration and catabolic activities of the bacterial community were examined in microcosm experiments. Four cultivars of Zea mays L. of two different isolines (each one including the conventional crop and its Bacillus thuringiensis cultivar) and one control of bulk soil were included in the experimental design. The growth models suggest a dichotomy between soils amended with either conventional or transgenic maize residues. The Cry1Ab protein appeared to influence the composition of the microbial community. The highly enhanced soil respiration observed during the first 72 h after the addition of Bt-maize residues can be interpreted as being related to the presence of the transgenic crop residues. This result was confirmed by agar plate counting, as the averages of the colony-forming units of soils in conventional treatments were about one-third of those treated with transgenic straw. Furthermore, the addition of Bt-maize appeared to induce increased microbial consumption of carbohydrates in BIOLOG EcoPlates. Three weeks after the addition of maize residues to the soils, no differences between the consumption rate of specific chemical guilds by bacteria in soils amended with transgenic maize and bacteria in soils amended with conventional maize were detectable. Reaped crop residues, comparable to post-harvest maize straw (a common practice in current agriculture), rapidly influence the soil bacterial cells at a functional level. Overall, these data support the existence of short

  3. Diagnosis of Ankylosing Spondylitis

    ... Reactive Arthritis Enteropathic Arthritis Blood Work and the HLA-B27 Test First, HLA-B27 is a perfectly normal gene found in 8% ... Secondly, it is important to note that the HLA-B27 test is not a diagnostic test for ankylosing ...

  4. Effect of Angiotensin(1-7) on Heart Function in an Experimental Rat Model of Obesity

    Blanke, Katja; Schlegel, Franziska; Raasch, Walter; Bader, Michael; Dähnert, Ingo; Dhein, Stefan; Salameh, Aida

    2015-01-01

    Aim: Obesity is a risk factor for the development of cardiovascular diseases. Recently it was shown that overexpression of the Mas-receptor antagonist angiotensin(1-7) could prevent from diet-induced obesity. However, it remained unclear whether diet-induced obesity and angiotensin(1-7) overexpression might also have effects on the cardiovascular system in these rats. Methods:Twenty three male Sprague Dawley rats were fed with standard chow (SD+chow, n = 5) or a cafeteria diet (SD+CD, n = 6) for 5 months. To investigate the effect of angiotensin(1-7) transgenic rats, expressing an angiotensin(1-7)-producing fusion protein in testis were used. These transgenic rats also received a 5 month's feeding period with either chow (TGR+chow, n = 6) or cafeteria diet (TGR+CD, n = 6), respectively. Hemodynamic measurements (pressure-volume loops) were carried out to assess cardiac function and blood pressure. Subsequently, hearts were explanted and investigated according to the Langendorff technique. Furthermore, cardiac remodeling in these animals was investigated histologically. Results:After 5 months cafeteria diet feeding rats showed a significantly increased body weight, which could be prevented in transgenic rats. However, there was no effect on cardiac performance after cafeteria diet in non-transgenic and transgenic rats. Moreover, overexpression of angiotensin(1-7) deteriorated cardiac contractility as indicated by impaired dp/dt. Furthermore, histological analysis revealed that cafeteria diet led to myocardial fibrosis in both, control and transgenic rats and this was not inhibited by an overproduction of angiotensin(1-7). Conclusion:These results indicate that an overexpression of circulating angiotensin(1-7) prevents a cafeteria diet-induced increase in body weight, but does not affect cardiac performance in this experimental rat model of obesity. Furthermore, overexpression of angiotensin(1-7) alone resulted in an impairment of cardiac function. PMID:26733884

  5. Efficient Generation of Mice with Consistent Transgene Expression by FEEST.

    Gao, Lei; Jiang, Yonghua; Mu, Libing; Liu, Yanbin; Wang, Fengchao; Wang, Peng; Zhang, Aiqun; Tang, Nan; Chen, Ting; Luo, Minmin; Yu, Lei; Gao, Shaorong; Chen, Liang

    2015-01-01

    Transgenic mouse models are widely used in biomedical research; however, current techniques for producing transgenic mice are limited due to the unpredictable nature of transgene expression. Here, we report a novel, highly efficient technique for the generation of transgenic mice with single-copy integration of the transgene and guaranteed expression of the gene-of-interest (GOI). We refer to this technique as functionally enriched ES cell transgenics, or FEEST. ES cells harboring an inducible Cre gene enabled the efficient selection of transgenic ES cell clones using hygromycin before Cre-mediated recombination. Expression of the GOI was confirmed by assaying for the GFP after Cre recombination. As a proof-of-principle, we produced a transgenic mouse line containing Cre-activatable tTA (cl-tTA6). This tTA mouse model was able to induce tumor formation when crossed with a transgenic mouse line containing a doxycycline-inducible oncogene. We also showed that the cl-tTA6 mouse is a valuable tool for faithfully recapitulating the clinical course of tumor development. We showed that FEEST can be easily adapted for other genes by preparing a transgenic mouse model of conditionally activatable EGFR L858R. Thus, FEEST is a technique with the potential to generate transgenic mouse models at a genome-wide scale. PMID:26573149

  6. Green Tea Polyphenols Control Dysregulated Glutamate Dehydrogenase in Transgenic Mice by Hijacking the ADP Activation Site

    Li, Changhong; Li, Ming; Chen, Pan; Narayan, Srinivas; Matschinsky, Franz M.; Bennett, Michael J.; Stanley, Charles A.; Smith, Thomas J. (CH-PA); (UPENN); (Danforth)

    2012-05-09

    Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate and, in animals, is extensively regulated by a number of metabolites. Gain of function mutations in GDH that abrogate GTP inhibition cause the hyperinsulinism/hyperammonemia syndrome (HHS), resulting in increased pancreatic {beta}-cell responsiveness to leucine and susceptibility to hypoglycemia following high protein meals. We have previously shown that two of the polyphenols from green tea (epigallocatechin gallate (EGCG) and epicatechin gallate (ECG)) inhibit GDH in vitro and that EGCG blocks GDH-mediated insulin secretion in wild type rat islets. Using structural and site-directed mutagenesis studies, we demonstrate that ECG binds to the same site as the allosteric regulator, ADP. Perifusion assays using pancreatic islets from transgenic mice expressing a human HHS form of GDH demonstrate that the hyperresponse to glutamine caused by dysregulated GDH is blocked by the addition of EGCG. As observed in HHS patients, these transgenic mice are hypersensitive to amino acid feeding, and this is abrogated by oral administration of EGCG prior to challenge. Finally, the low basal blood glucose level in the HHS mouse model is improved upon chronic administration of EGCG. These results suggest that this common natural product or some derivative thereof may prove useful in controlling this genetic disorder. Of broader clinical implication is that other groups have shown that restriction of glutamine catabolism via these GDH inhibitors can be useful in treating various tumors. This HHS transgenic mouse model offers a highly useful means to test these agents in vivo.

  7. Temporal and spatial patterns of transgene expression in aging adult mice provide insights about the origins, organization, and differentiation of the intestinal epithelium.

    Cohn, S. M.; Roth, K A; Birkenmeier, E H; Gordon, J I

    1991-01-01

    We have used liver fatty acid-binding protein/human growth hormone (L-FABP/hGH) fusion genes to explore the temporal and spatial differentiation of intestinal epithelial cells in 1- to 12-month-old transgenic mice. The intact, endogenous L-FABP gene (Fabpl) was not expressed in the colon at any time. Young adult transgenic mice containing nucleotides -596 to +21 of the rat L-FABP gene linked to the hGH gene (minus its 5' nontranscribed domain) demonstrated inappropriate expression of hGH in e...

  8. Transgenic arthropods and the sterile insect technique

    The Sterile Insect Technique can benefit from transgenesis in three ways by creating; (1) genetically marked strains, (2) genetic sexing strains and (3) strains that induce molecular sterility in the field. Experience with the development of genetic sexing strains based on indicates that caution is required during the experimental evaluation of any potential transgenic strain. Two major scientific concerns involve the overall fitness of transgenic strains and their stability over time. The latter being very important especially when the extremely large numbers of insects that are mass reared is taken into account. Currently transformation events are random and it will probably be necessary to select suitable strains from many that are induced. The success of transformation itself in many insect species will enable many new strategies to be developed and tested. (author)

  9. A multidisciplinary approach involving comparative 'OMICS' of transgenic and non-transgenic soybeam seeds

    Complete text of publication follows. Soybean culture has an expressive impact in the economy of many countries, being the commercialization of its by-products, which presents many benefits in terms of health and nutritional aspects, and which also includes a fuel alternative (biodiesel), the main factor for the large soybean production. Part of this impact is due to the transgenic modification of soybean, conferring enhanced characteristics to the culture, such as tolerance to fungicides (Y. Kim et al., J. Microbiol. Biotechnol., 16 (2006), 25-31.). Due to the insertion of hexogen genes, some proteome modification is possible (S. Natarajan et al., Anal. Biochem., 342 (2005), 214-220), and recently some metallome modification was reported by our research group (A. Sussulini et al., J. Anal. At. Spectrom., 22 (2007), 1501-1506). Then, the aim of this work is to enlarge the results in terms of 'omics' when considering transgenic and non-transgenic soybean seeds. For this task, the identification of more than 140 soybean proteins using MALDI-QTOF-MS after 2D-PAGE protein separation (369±46 and 376±42 protein spots in the 4-7 pI range for transgenic and non-transgenic soybean seeds, respectively), the analysis of the protein expression using image program, the analysis of some enzymes (SOD, GR, APX, CAT) involved in the ROS production, the mapping of 80 protein spots using SR-XRF, and the metal identification of more than 30 spots using ICP-MS was carried out. In terms of metal distribution when considering some proteins, the results displayed a great ability of proteins bind different metal ions. High iron (sucrose binding protein homolog S-64 - 57,922 kDa), chromium (protein not identified), lead (seed maturation protein PM 41 - 15,103 kDa), copper and tin (trypsin inhibitor (kunitz), chain A - 20,417 kDa) contents were achieved in the non-transgenic soybean, while high magnesium (actin - 50,281 kDa), barium (protein not identified) and ruthenium (protein not

  10. Toxins for Transgenic Resistance to Hemipteran Pests

    Bryony C. Bonning; Chougule, Nanasaheb P.

    2012-01-01

    The sap sucking insects (Hemiptera), which include aphids, whiteflies, plant bugs and stink bugs, have emerged as major agricultural pests. The Hemiptera cause direct damage by feeding on crops, and in some cases indirect damage by transmission of plant viruses. Current management relies almost exclusively on application of classical chemical insecticides. While the development of transgenic crops expressing toxins derived from the bacterium Bacillus thuringiensis (Bt) ha...

  11. Phytoremediation of polychlorinated biphenyls by transgenic tobacco

    Chrastilová, Z.; Macková, M.; Nováková, M.; Szekeres, M.; Macek, Tomáš

    Chania: Technical University of Crete, 2008 - (Kalogerakis, N.; Fava, F.; Banwart, S.). s. 295-295 ISBN 978-960-8475-12-0. [European Bioremediation Conference /4./. 03.09.2008-06.09.2008, Chania] R&D Projects: GA MŠk 1M06030 Institutional research plan: CEZ:AV0Z40550506 Keywords : phytoremediation * PCB * transgenic plants * bphC Subject RIV: EI - Biotechnology ; Bionics

  12. Transgenic nonhuman primates for neurodegenerative diseases

    Chan Anthony WS

    2004-06-01

    Full Text Available Abstract Animal models that represent human diseases constitute an important tool in understanding the pathogenesis of the diseases, and in developing effective therapies. Neurodegenerative diseases are complex disorders involving neuropathologic and psychiatric alterations. Although transgenic and knock-in mouse models of Alzheimer's disease, (AD, Parkinson's disease (PD and Huntington's disease (HD have been created, limited representation in clinical aspects has been recognized and the rodent models lack true neurodegeneration. Chemical induction of HD and PD in nonhuman primates (NHP has been reported, however, the role of intrinsic genetic factors in the development of the diseases is indeterminable. Nonhuman primates closely parallel humans with regard to genetic, neuroanatomic, and cognitive/behavioral characteristics. Accordingly, the development of NHP models for neurodegenerative diseases holds greater promise for success in the discovery of diagnoses, treatments, and cures than approaches using other animal species. Therefore, a transgenic NHP carrying a mutant gene similar to that of patients will help to clarify our understanding of disease onset and progression. Additionally, monitoring disease onset and development in the transgenic NHP by high resolution brain imaging technology such as MRI, and behavioral and cognitive testing can all be carried out simultaneously in the NHP but not in other animal models. Moreover, because of the similarity in motor repertoire between NHPs and humans, it will also be possible to compare the neurologic syndrome observed in the NHP model to that in patients. Understanding the correlation between genetic defects and physiologic changes (e.g. oxidative damage will lead to a better understanding of disease progression and the development of patient treatments, medications and preventive approaches for high risk individuals. The impact of the transgenic NHP model in understanding the role which

  13. Melanosis and associated tumors in transgenic mice.

    Klein-Szanto, A.; Bradl, M; Porter, S; Mintz, B

    1991-01-01

    Melanosis was found to various extents in a wide array of tissues of all 23 autopsied mice whose transgene consisted of the tyrosinase promoter fused to the simian virus 40 early-region oncogenic sequences. Pigmentation in a given animal was attributable to any or all of the following; an increase in numbers of some normally pigmented cells of neural crest origin (a result compatible with early stages of transformation); elicitation of melanin synthesis in some cells that normally have little...

  14. Review and prospect of transgenic rice research

    CHEN Hao; LIN YongJun; ZHANG QiFa

    2009-01-01

    Rice is one of the most important crops as the staple food for more than half of the world's population.Rice improvement has achieved remarkable success in the past half-century,with the yield doubled in most parts of the world and even tripled in certain regions,which has contributed greatly to food security globally.Rapid population growth and economic development pose a constantly increased food requirement.However,rice yield has been hovering in the past decade,which is mainly caused by the absence of novel breeding technologies,reduction of genetic diversity of rice cultivars,and serious yield loss due to increasingly severe occurrences of insects,diseases,and abiotic stresses.To address these challenges,Chinese scientists proposed a novel rice breeding goal of developing Green Super Rice to improve rice varieties and realize the sustainable development of agriculture,by focusing on the following 5 classes of traits:insect and disease resistance,drought-tolerance,nutrient-use efficiency,quality and yield potential.As a modern breeding approach,transgenic strategy will play an important role in realizing the goal of Green Super Rice.Presently,many transgenic studies of rice have been conducted,and most of target traits are consistent with the goal of Green Super Rice.In this paper,we firstly review technical advances of rice transformation,and then outline the main progress in transgenic rice research with respect to the most important traits:insect and disease-resistance,drought-tolerance,nutrient-use efficiency,quality,yield potential and herbicide-tolerance.The prospects of developing transgenic rice are also discussed.

  15. Genotypic and phenotypic characterization of P23H line 1 rat model.

    Elise Orhan

    Full Text Available Rod-cone dystrophy, also known as retinitis pigmentosa (RP, is the most common inherited degenerative photoreceptor disease, for which no therapy is currently available. The P23H rat is one of the most commonly used autosomal dominant RP models. It has been created by incorporation of a mutated mouse rhodopsin (Rho transgene in the wild-type (WT Sprague Dawley rat. Detailed genetic characterization of this transgenic animal has however never been fully reported. Here we filled this knowledge gap on P23H Line 1 rat (P23H-1 and provide additional phenotypic information applying non-invasive and state-of-the-art in vivo techniques that are relevant for preclinical therapeutic evaluations. Transgene sequence was analyzed by Sanger sequencing. Using quantitative PCR, transgene copy number was calculated and its expression measured in retinal tissue. Full field electroretinography (ERG and spectral domain optical coherence tomography (SD-OCT were performed at 1-, 2-, 3- and 6-months of age. Sanger sequencing revealed that P23H-1 rat carries the mutated mouse genomic Rho sequence from the promoter to the 3' UTR. Transgene copy numbers were estimated at 9 and 18 copies in the hemizygous and homozygous rats respectively. In 1-month-old hemizygous P23H-1 rats, transgene expression represented 43% of all Rho expressed alleles. ERG showed a progressive rod-cone dysfunction peaking at 6 months-of-age. SD-OCT confirmed a progressive thinning of the photoreceptor cell layer leading to the disappearance of the outer retina by 6 months with additional morphological changes in the inner retinal cell layers in hemizygous P23H-1 rats. These results provide precise genotypic information of the P23H-1 rat with additional phenotypic characterization that will serve basis for therapeutic interventions, especially for those aiming at gene editing.

  16. Transgenic oil palm: production and projection.

    Parveez, G K; Masri, M M; Zainal, A; Majid, N A; Yunus, A M; Fadilah, H H; Rasid, O; Cheah, S C

    2000-12-01

    Oil palm is an important economic crop for Malaysia. Genetic engineering could be applied to produce transgenic oil palms with high value-added fatty acids and novel products to ensure the sustainability of the palm oil industry. Establishment of a reliable transformation and regeneration system is essential for genetic engineering. Biolistic was initially chosen as the method for oil palm transformation as it has been the most successful method for monocotyledons to date. Optimization of physical and biological parameters, including testing of promoters and selective agents, was carried out as a prerequisite for stable transformation. This has resulted in the successful transfer of reporter genes into oil palm and the regeneration of transgenic oil palm, thus making it possible to improve the oil palm through genetic engineering. Besides application of the Biolistics method, studies on transformation mediated by Agrobacterium and utilization of the green fluorescent protein gene as a selectable marker gene have been initiated. Upon the development of a reliable transformation system, a number of useful targets are being projected for oil palm improvement. Among these targets are high-oleate and high-stearate oils, and the production of industrial feedstock such as biodegradable plastics. The efforts in oil palm genetic engineering are thus not targeted as commodity palm oil. Due to the long life cycle of the palm and the time taken to regenerate plants in tissue culture, it is envisaged that commercial planting of transgenic palms will not occur any earlier than the year 2020. PMID:11171275

  17. Compensation of the AKT signaling by ERK signaling in transgenic mice hearts overexpressing TRIM72

    The AKT and ERK signaling pathways are known to be involved in cell hypertrophy, proliferation, survival and differentiation. Although there is evidence for crosstalk between these two signaling pathways in cellulo, there is less evidence for cross talk in vivo. Here, we show that crosstalk between AKT and ERK signaling in the hearts of TRIM72-overexpressing transgenic mice (TRIM72-Tg) with alpha-MHC promoter regulates and maintains their heart size. TRIM72, a heart- and skeletal muscle-specific protein, downregulates AKT-mTOR signaling via IRS-1 degradation and reduces the size of rat cardiomyocytes and the size of postnatal TRIM72-Tg hearts. TRIM72 expression was upregulated by hypertrophic inducers in cardiomyocytes, while IRS-1 was downregulated by IGF-1. TRIM72 specifically regulated IGF-1-dependent AKT-mTOR signaling, resulting in a reduction of the size of cardiomyocytes. Postnatal TRIM72-Tg hearts were smaller than control-treated hearts with inhibition of AKT-mTOR signaling. However, adult TRIM72-Tg hearts were larger than of control despite the suppression of AKT-mTOR signaling. Activation of ERK, PKC-α, and JNK were observed to be elevated in adult TRIM72-Tg, and these signals were mediated by ET-1 via the ET receptors A and B. Altogether, these results suggest that AKT signaling regulates cardiac hypertrophy in physiological conditions, and ERK signaling compensates for the absence of AKT signaling during TRIM72 overexpression, leading to pathological hypertrophy. -- Highlights: • TRIM72 inhibits AKT signaling through ubiquitination of IRS-1 in cardiac cells. • TRIM72 regulates the size of cardiac cells. • TRIM72 regulates size of postnatal TRIM72-overexpressing transgenic mice hearts. • Adult TRIM72-overexpressing transgenic mice hearts showed cardiac dysfunction. • Adult TRIM72 transgenic mice hearts showed higher expression of endothelin receptors

  18. Compensation of the AKT signaling by ERK signaling in transgenic mice hearts overexpressing TRIM72

    Ham, Young-Mi, E-mail: youngmi_ham@hms.harvard.edu [College of Life Science and Biotechnology, Korea University, Seoul (Korea, Republic of); Department of Cell Biology, Harvard Medical School, Boston, MA 02115 (United States); Mahoney, Sarah Jane [Department of Cell Biology, Harvard Medical School, Boston, MA 02115 (United States)

    2013-06-10

    The AKT and ERK signaling pathways are known to be involved in cell hypertrophy, proliferation, survival and differentiation. Although there is evidence for crosstalk between these two signaling pathways in cellulo, there is less evidence for cross talk in vivo. Here, we show that crosstalk between AKT and ERK signaling in the hearts of TRIM72-overexpressing transgenic mice (TRIM72-Tg) with alpha-MHC promoter regulates and maintains their heart size. TRIM72, a heart- and skeletal muscle-specific protein, downregulates AKT-mTOR signaling via IRS-1 degradation and reduces the size of rat cardiomyocytes and the size of postnatal TRIM72-Tg hearts. TRIM72 expression was upregulated by hypertrophic inducers in cardiomyocytes, while IRS-1 was downregulated by IGF-1. TRIM72 specifically regulated IGF-1-dependent AKT-mTOR signaling, resulting in a reduction of the size of cardiomyocytes. Postnatal TRIM72-Tg hearts were smaller than control-treated hearts with inhibition of AKT-mTOR signaling. However, adult TRIM72-Tg hearts were larger than of control despite the suppression of AKT-mTOR signaling. Activation of ERK, PKC-α, and JNK were observed to be elevated in adult TRIM72-Tg, and these signals were mediated by ET-1 via the ET receptors A and B. Altogether, these results suggest that AKT signaling regulates cardiac hypertrophy in physiological conditions, and ERK signaling compensates for the absence of AKT signaling during TRIM72 overexpression, leading to pathological hypertrophy. -- Highlights: • TRIM72 inhibits AKT signaling through ubiquitination of IRS-1 in cardiac cells. • TRIM72 regulates the size of cardiac cells. • TRIM72 regulates size of postnatal TRIM72-overexpressing transgenic mice hearts. • Adult TRIM72-overexpressing transgenic mice hearts showed cardiac dysfunction. • Adult TRIM72 transgenic mice hearts showed higher expression of endothelin receptors.

  19. FTY720 Attenuates Acute Pancreatitis in Hypertriglyceridemic Apolipoprotein CIII Transgenic Mice.

    Liu, Jinjiao; Xu, Pengfei; Zhang, Ling; Kayoumu, Abudurexiti; Wang, Yunan; Wang, Mengyu; Gao, Mingming; Zhang, Xiaohong; Wang, Yuhui; Liu, George

    2015-09-01

    Hypertriglyceridemic pancreatitis (HTGP) is often encountered clinically as a common form of recurrent acute pancreatitis (AP). It is important to evaluate the management of severe hypertriglyceridemia (HTG) or anti-inflammation in the prophylaxis of HTGP in the clinic. FTY720 (2-amino-2[2-(4-octylphenyl) ethyl]-1, 3-propanediol) is a new anti-inflammatory agent with low toxicity and reported to ameliorate lung injury with pancreatitis in rat. We evaluated its protective affection on AP induced by seven hourly intraperitoneal injection of cerulein in apolipoprotein CIII transgenic mice with severe HTG. FTY720 at 1.5 mg/kg was administered by gastric lavage daily for 3 days before induction of AP. The effects of FTY720 to protect against HTGP were assessed by serum amylase, pancreatic pathological scores, immunostaining, and the expression of inflammatory cytokine genes. As a result, injection of cerulein resulted in more severe pathological changes of AP and higher monocyte chemoattractant protein 1 expression in the pancreas in transgenic than in nontransgenic mice. FTY720 pretreatment improved the pathological severity of AP and decreased the expression of monocyte chemoattractant protein 1 in the pancreas significantly, especially near fourfold reduction in transgenic mice. However, FTY720 did not affect plasma triglyceride levels, and other inflammatory factors and plasma amylase were not correlated with the extent of pancreatic damage in AP with or without FTY720 administration. In summary, our study in a new model, apolipoprotein CIII transgenic mice, demonstrated that HTG mice are susceptible to induction of AP. Prophylactic treatment of FTY720 can significantly attenuate cerulein-induced AP and hence warrant further investigation of sphingosine-1-phosphate receptors agonist for potential clinical application in recurrent attacks of HTGP. PMID:25944794

  20. In situ methods to localize transgenes and transcripts in interphase nuclei: a tool for transgenic plant research

    Shaw Peter

    2006-11-01

    Full Text Available Abstract Genetic engineering of commercially important crops has become routine in many laboratories. However, the inability to predict where a transgene will integrate and to efficiently select plants with stable levels of transgenic expression remains a limitation of this technology. Fluorescence in situ hybridization (FISH is a powerful technique that can be used to visualize transgene integration sites and provide a better understanding of transgene behavior. Studies using FISH to characterize transgene integration have focused primarily on metaphase chromosomes, because the number and position of integration sites on the chromosomes are more easily determined at this stage. However gene (and transgene expression occurs mainly during interphase. In order to accurately predict the activity of a transgene, it is critical to understand its location and dynamics in the three-dimensional interphase nucleus. We and others have developed in situ methods to visualize transgenes (including single copy genes and their transcripts during interphase from different tissues and plant species. These techniques reduce the time necessary for characterization of transgene integration by eliminating the need for time-consuming segregation analysis, and extend characterization to the interphase nucleus, thus increasing the likelihood of accurate prediction of transgene activity. Furthermore, this approach is useful for studying nuclear organization and the dynamics of genes and chromatin.