Sample records for ataxic cacna1a-mutant mouse

  1. Enzyme replacement improves ataxic gait and central nervous system histopathology in a mouse model of metachromatic leukodystrophy.

    Matzner, Ulrich; Lüllmann-Rauch, Renate; Stroobants, Stijn; Andersson, Claes; Weigelt, Cecilia; Eistrup, Carl; Fogh, Jens; D'Hooge, Rudi; Gieselmann, Volkmar


    Inherited deficiencies of lysosomal hydrolases cause lysosomal storage diseases (LSDs) that are characterized by a progressive multisystemic pathology and premature death. Repeated intravenous injection of the active counterpart of the deficient enzyme, a treatment strategy called enzyme replacement therapy (ERT), evolved as a clinical option for several LSDs without central nervous system (CNS) involvement. To assess the efficacy of long-term ERT in metachromatic leukodystrophy (MLD), an LSD with prevailing nervous system disease, we treated immunotolerant arylsulfatase A (ASA) knockout mice with 52 doses of either 4 or 50 mg/kg recombinant human ASA (rhASA). ERT was tolerated without side effects and improved disease manifestations in a dose-dependent manner. Dosing of 4 mg/kg diminished sulfatide storage in kidney and peripheral nervous system (PNS) but not the CNS, whereas treatment with 50 mg/kg was also effective in the CNS in reducing storage in brain and spinal cord by 34 and 45%, respectively. Histological analyses revealed regional differences in sulfatide clearance. While 70% less storage profiles were detectable, for example, in the hippocampal fimbria, the histopathology of the brain stem was unchanged. Both enzyme doses normalized the ataxic gait of ASA knockout mice, demonstrating prevention of nervous system dysfunctions that dominate early stages of MLD. PMID:19174759

  2. 4 cases of 'ataxic hemiparesis'

    Ataxic hemiparesis is described as a syndrome in which pyramidal and cerebellar signs occur ipsilaterally. Fisher who suggestd the designation ''ataxic hemiparesis'' for this syndrome confirmed by pathological study that causative lesion was in the basis pontis at the level of the junction of the upper one third and lower two thirds on the opposite side of the neurological deficit and he also reported that CT might fail to show the lesion. We observed 4 patients with ataxic hemiparesis and examined them in auditory brainstem response (ABR), somatosensory evoked potential (SEP), and blink reflex as electrophysiological study. Their CT and electrophysiological findings were compared with each others to define the responsible lesion more clearly. Essentially, these abnormal electrophysiological findings were recognized only in the case of pontine hemorrhage, and these findings recovered to normal as clinical and CT findings were improved. In the other cases, the electrophysiological findings were not prominent and CT revealed the lesions in deep frontal region, internal capsule and cerebellar hemispheres respectively. These results might show that many cases of extra-pontine lesions could develop the syndrome of ataxic hemiparesis. However, the relation between responsible lesions for ataxic hemiparesis and electrophysiological findings are still uncertain. Further evidences including clinicopathological studies will be required to clarify this relation and to get the more accurate anatomical interpretation of ataxic hemiparesis from lesions besides the pontine region. (author)

  3. From mice to men: lessons from mutant ataxic mice

    Cendelin, Jan


    Ataxic mutant mice can be used to represent models of cerebellar degenerative disorders. They serve for investigation of cerebellar function, pathogenesis of degenerative processes as well as of therapeutic approaches. Lurcher, Hot-foot, Purkinje cell degeneration, Nervous, Staggerer, Weaver, Reeler, and Scrambler mouse models and mouse models of SCA1, SCA2, SCA3, SCA6, SCA7, SCA23, DRPLA, Niemann-Pick disease and Friedreich ataxia are reviewed with special regard to cerebellar pathology, pat...

  4. Ataxic cerebral palsy and genetic predisposition.

    Miller, G.


    It was calculated that in the 962 family members of 36 patients with ataxic cerebral palsy there were 75 (8%) with a history of neurodevelopmental disorder and 31 (3%) with a major congenital malformation. This was not significantly greater than expected, and does not support the hypothesis of a genetic non-Mendelian role in the aetiology of ataxic cerebral palsy.

  5. Minor congenital anomalies and ataxic cerebral palsy.

    Miller, G


    The incidence of minor congenital anomalies was examined in 36 patients with ataxic cerebral palsy, in unaffected family members, and in 100 unrelated control subjects. None of the control subjects or family members had more than four anomalies, and 25 of 36 (69%) of the patients had more than four. The distribution of anomalies differed considerably, with 60% of the index cases having seven or more, and 94% of the controls having three or less. The number occurring in the patients was signif...

  6. Acoustic Characteristics of Ataxic Speech in Japanese Patients with Spinocerebellar Degeneration (SCD)

    Ikui, Yukiko; Tsukuda, Mamoru; Kuroiwa, Yoshiyuki; Koyano, Shigeru; Hirose, Hajime; Taguchi, Takahide


    Background: In English- and German-speaking countries, ataxic speech is often described as showing scanning based on acoustic impressions. Although the term "scanning" is generally considered to represent abnormal speech features including prosodic excess or insufficiency, any precise acoustic analysis of ataxic speech has not been performed in…

  7. Therapeutic Intervention in a Case of Ataxic Dysarthria Associated with a History of Amateur Boxing

    McMicken, Betty L.; Ostergren, Jennifer A.; Vento-Wilson, Margaret


    The goals of this study were to (a) describe the presenting features of ataxic dysarthria present in a participant with a long history of amateur boxing, (b) describe a novel application of behavioral principles in the treatment of this participant, and (c) discuss implications in the treatment of ataxic dysarthria secondary to boxing. The…

  8. Clinical assessment of standing and gait in ataxic patients using a triaxial accelerometer

    Matsushima, Akira; Yoshida, Kunihiro; Genno, Hirokazu; Murata, Asuka; Matsuzawa, Setsuko; Nakamura, Katsuya; Nakamura, Akinori; Ikeda, Shu-ichi


    Background The aim of this study was to investigate the usefulness of a triaxial accelerometer for the clinical assessment of standing and gait impairment in ataxic patients quantitatively. Fifty-one patients with spinocerebellar ataxia (SCA) or multiple system atrophy with predominant cerebellar ataxia (MSA-C) and 56 healthy control subjects were enrolled. The subjects, with a triaxial accelerometer on their back, were indicated to stand for 30 s in four different conditions (eyes opened or ...

  9. The Effects of Topic Knowledge on Intelligibility and Lexical Segmentation in Hypokinetic and Ataxic Dysarthria

    Rene L. Utianski; Lansford, Kaitlin L.; Liss, Julie M.; Azuma, Tamiko


    Benefits to speech intelligibility can be achieved by enhancing a listener’s ability to decipher it. However, much remains to be learned about the variables that influence the effectiveness of various listener-based manipulations. This study examined the benefit of providing listeners with the topic of some phases produced by speakers with either hypokinetic or ataxic dysarthria. Total and topic word accuracy, topic-related substitutions, and lexical boundary errors were calculated from the l...

  10. The effects of familiarization on intelligibility and lexical segmentation in hypokinetic and ataxic dysarthria

    Liss, Julie M.; Spitzer, Stephanie M.; Caviness, John N.; Adler, Charles


    This study is the third in a series that has explored the source of intelligibility decrement in dysarthria by jointly considering signal characteristics and the cognitive-perceptual processes employed by listeners. A paradigm of lexical boundary error analysis was used to examine this interface by manipulating listener constraints with a brief familiarization procedure. If familiarization allows listeners to extract relevant segmental and suprasegmental information from dysarthric speech, they should obtain higher intelligibility scores than nonfamiliarized listeners, and their lexical boundary error patterns should approximate those obtained in misperceptions of normal speech. Listeners transcribed phrases produced by speakers with either hypokinetic or ataxic dysarthria after being familiarized with other phrases produced by these speakers. Data were compared to those of nonfamiliarized listeners [Liss et al., J. Acoust. Soc. Am. 107, 3415-3424 (2000)]. The familiarized groups obtained higher intelligibility scores than nonfamiliarized groups, and the effects were greater when the dysarthria type of the familiarization procedure matched the dysarthria type of the transcription task. Remarkably, no differences in lexical boundary error patterns were discovered between the familiarized and nonfamiliarized groups. Transcribers of the ataxic speech appeared to have difficulty distinguishing strong and weak syllables in spite of the familiarization. Results suggest that intelligibility decrements arise from the perceptual challenges posed by the degraded segmental and suprasegmental aspects of the signal, but that this type of familiarization process may differentially facilitate mapping segmental information onto existing phonological categories.

  11. Speech serial control in healthy speakers and speakers with hypokinetic or ataxic dysarthria: Effects of sequence length and practice

    Kevin J Reilly


    Full Text Available The current study investigated the processes responsible for selection of sounds and syllables during production of speech sequences in 10 adults with hypokinetic dysarthria from Parkinson’s disease, 5 adults with ataxic dysarthria, and 14 healthy control speakers. Speech production data from a choice reaction time task were analyzed to evaluate the effects of sequence length and practice on speech sound sequencing. Speakers produced sequences that were between one and five syllables in length over five experimental runs of 60 trials each. In contrast to the healthy speakers, speakers with hypokinetic dysarthria demonstrated exaggerated sequence length effects for both inter-syllable intervals (ISIs and speech error rates. Conversely, speakers with ataxic dysarthria failed to demonstrate a sequence length effect on ISIs and were also the only group that did not exhibit practice-related changes in ISIs and speech error rates over the five experimental runs. The exaggerated sequence length effects in the hypokinetic speakers with Parkinson’s disease are consistent with an impairment of action selection during speech sequence production. The absent length effects observed in the speakers with ataxic dysarthria is consistent with previous findings that indicate a limited capacity to buffer speech sequences in advance of their execution. In addition, the lack of practice effects in these speakers suggests that learning-related improvements in the production rate and accuracy of speech sequences involves processing by structures of the cerebellum. Together, the current findings inform models of serial control for speech in healthy speakers and support the notion that sequencing deficits contribute to speech symptoms in speakers with hypokinetic or ataxic dysarthria. In addition, these findings indicate that speech sequencing is differentially impaired in hypokinetic and ataxic dysarthria.

  12. Radiographic and myelographic examination of the cervical vertebral column in 306 ataxic horses

    This study consists of a review of 306 ataxic horses subjected to survey radiography and myelography of the cervical vertebral column. Fifty-eight percent of horses had evidence of compressive spinal cord lesion on myelography. Sixty-six percent of horses were less than 3 years old. Age had no effect on the distribution of spinal cord compressive lesions. No conclusion could be drawn from sex and breed distribution. The most common sites of cord compression on myelography in order of decreasing frequency were C3–4, C6–7, C5–6, and C4–5. Twenty-nine percent of horses with myelographic evidence of cord compression had multiple compressive sites. Survey radiographs were not reliable to diagnose compressive spinal cord lesions. Myelography was a safe and more accurate procedure. Several factors may result in misinterpretation of the myelographic examination

  13. Spinocerebellar ataxias type 8, 12, and 17 and dentatorubro-pallidoluysian atrophy in Czech ataxic patients.

    Musova, Zuzana; Sedlacek, Zdenek; Mazanec, Radim; Klempir, Jiri; Roth, Jan; Plevova, Pavlina; Vyhnalek, Martin; Kopeckova, Marta; Apltova, Ludmila; Krepelova, Anna; Zumrova, Alena


    Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders currently associated with 27 genes. The most frequent types are caused by expansions in coding CAG repeats. The frequency of SCA subtypes varies among populations. We examined the occurrence of rare SCAs, SCA8, SCA12, SCA17 and dentatorubro-pallidoluysian atrophy (DRPLA), in the Czech population from where the data were missing. We analyzed causal gene expansions in 515 familial and sporadic ataxic patients negatively tested for SCA1-3 and SCA6-7. Pathogenic SCA8 and SCA17 expansions were identified in eight and five patients, respectively. Tay-Sachs disease was later diagnosed in one patient with an SCA8 expansion and the diagnosis of multiple sclerosis (MS) was suspected in two other patients with SCA8 expansions. These findings are probably coincidental, although the participation of SCA8 expansions in the susceptibility to MS and disease progression cannot be fully excluded. None of the patients had pathogenic SCA12 or DRPLA expansions. However, three patients had intermediate SCA12 alleles out of the normal range with 36 and 43 CAGs. Amyotrophic lateral sclerosis (ALS) was probable in the patient with 43 CAGs. This coincidence is remarkable, especially in the context with the recently identified predisposing role of longer SCA2 alleles in ALS. Five families with SCA17 represent a significant portion of ataxic patients and this should be reflected in the diagnostics of SCAs in the Czech population. SCA8 expansions must be considered after careful clinical evaluation. PMID:22872568

  14. Bilateral Vestibulopathy Aggravates Balance and Gait Disturbances in Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis: A Case Report.

    van Leeuwen, Roeland B; Smits, Bart W; Rodenburg, Richard J; van Engelen, Baziel G


    In patients with a triad of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO), the presenting features are mainly ataxia or ptosis. SANDO patients often have impaired balance and gait, which is not surprising considering the combination of sensory ataxic neuropathy, and additional symptoms like cerebellar ataxia and limb girdle weakness. We describe a SANDO patient who noticed an increasingly impaired balance and gait, without any dizziness. Neurological investigation revealed an external ophthalmeplegia and a cerebellar ataxia; the head impulse test was not reliable because of eye movement disorders. The caloric reflex tests showed lack of responses on both sides, compatible with severe bilateral vestibulopathy. Making the diagnosis of bilateral vestibulopathy in SANDO patients may have implications for the management of the patient, because specific vestibular rehabilitation can improve gaze and postural stability. PMID:27552387

  15. Diffusion tensor imaging of the cortico-ponto-cerebellar pathway in patients with adult-onset ataxic neurodegenerative disease

    Kitamura, Kaeko; Nakayama, Keiko; Yamada, Eiji; Inoue, Yuichi [Osaka City University Graduate School of Medicine, Department of Radiology, Osaka (Japan); Kosaka, Satoru; Shimada, Hiroyuki; Miki, Takami [Osaka City University Graduate School of Medicine, Department of Neurology, Osaka (Japan)


    We sought to determine whether diffusion-tensor imaging (DTI) can detect in vivo axonal damage in the corticopontocerebellar pathway of patients with adult-onset ataxic neurodegenerative disease. Conventional MRI and DTI were performed on 18 patients with adult-onset ataxic neurodegenerative disease and 28 age-matched control subjects. Fractional anisotropy (FA) and the mean diffusivity (MD) were measured in the ventral, central, and dorsal pons, middle cerebellar peduncle (MCP) and internal capsule to evaluate corticopontocerebellar projection. Changes in FA and MD values were compared between patients and controls. Clinical disability was assessed according to the International Cooperative Ataxia Rating Scale (ICARS). The relationship between DTI measurements and ICARS was studied. Follow-up MRI was performed in five patients approximately 1 year later. FA values were significantly lower in the ventral and central portions of the pons, MCP, and internal capsules than in these areas in control subjects (P < 0.05) with the lower FA values correlating with poorer ICARS (r > -0.57, P < 0.05). MD values were elevated in these areas, but the differences were smaller than for the FA values. No relationship was observed between the MD and ICARS. In the five patients who underwent the follow-up study, there were significant decreases between the initial study and the follow-up DTI study for FA in the MCP and internal capsule (P < 0.05). DTI can demonstrate a degenerated corticopontocerebellar pathway in patients, and FA values can be correlated with ataxia severity. DTI may be a clinically useful tool as a quantitative surrogate marker for monitoring disease progression. (orig.)

  16. Expression of Caytaxin protein in Cayman Ataxia mouse models correlates with phenotype severity.

    Kristine M Sikora

    Full Text Available Caytaxin is a highly-conserved protein, which is encoded by the Atcay/ATCAY gene. Mutations in Atcay/ATCAY have been identified as causative of cerebellar disorders such as the rare hereditary disease Cayman ataxia in humans, generalized dystonia in the dystonic (dt rat, and marked motor defects in three ataxic mouse lines. While several lines of evidence suggest that Caytaxin plays a critical role in maintaining nervous system processes, the physiological function of Caytaxin has not been fully characterized. In the study presented here, we generated novel specific monoclonal antibodies against full-length Caytaxin to examine endogenous Caytaxin expression in wild type and Atcay mutant mouse lines. Caytaxin protein is absent from brain tissues in the two severely ataxic Atcay(jit (jittery and Atcay(swd (sidewinder mutant lines, and markedly decreased in the mildly ataxic/dystonic Atcay(ji-hes (hesitant line, indicating a correlation between Caytaxin expression and disease severity. As the expression of wild type human Caytaxin in mutant sidewinder and jittery mice rescues the ataxic phenotype, Caytaxin's physiological function appears to be conserved between the human and mouse orthologs. Across multiple species and in several neuronal cell lines Caytaxin is expressed as several protein isoforms, the two largest of which are caused by the usage of conserved methionine translation start sites. The work described in this manuscript presents an initial characterization of the Caytaxin protein and its expression in wild type and several mutant mouse models. Utilizing these animal models of human Cayman Ataxia will now allow an in-depth analysis to elucidate Caytaxin's role in maintaining normal neuronal function.

  17. Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) in a sibling pair with a homozygous p.A467T POLG mutation.

    McHugh, John C


    Two siblings who developed fifth-decade-onset, concurrent progressive sensory ataxia, dysarthria, and ophthalmoparesis were found to be homozygous for the p.A467T mutation of the polymerase gamma (POLG) gene. The clinical course in both subjects was progression to severe disability. The enlarging spectrum of sensory ataxic neuropathies associated with mitochondrial DNA (mtDNA) instability and POLG mutations should be recognized and considered in the differential diagnosis of this unusual presentation.

  18. Mouse model of intracerebellar haemorrhage.

    Tijjani Salihu, Abubakar; Muthuraju, Sangu; Aziz Mohamed Yusoff, Abdul; Ahmad, Farizan; Zulkifli Mustafa, Mohd; Jaafar, Hasnan; Idris, Zamzuri; Rahman Izaini Ghani, Abdul; Malin Abdullah, Jafri


    The present study aimed to investigate the behavior and neuronal morphological changes in the perihaemorrhagic tissue of the mouse intracerebellar haemorrhage experimental model. Adult male Swiss albino mice were stereotactically infused with collagenase type VII (0.4U/μl of saline) unilaterally in to the cerebellum, following anaesthesia. Motor deficits were assessed using open field and composite score for evaluating the mouse model of cerebellar ataxia at 1, 3, 7, 14 and 21 days after collagenase infusion. The animals were sacrificed at the same time interval for evaluation of perihaematomal neuronal degeneration using haematoxylin and eosin staining and Annexin V-FITC/Propidium iodide assay. At the end of the study, it was found that infusion of 0.4U collagenase produces significant locomotor and ataxic deficit in the mice especially within the first week post surgery, and that this gradually improved within three weeks. Neuronal degeneration evident by cytoplasmic shrinkage and nuclear pyknosis was observed at the perihaematomal area after one day; especially at 3 and 7 days post haemorrhage. By 21 days, both the haematoma and degenerating neurons in the perihaematomal area were phagocytosed and the remaining neuronal cells around the scar tissue appeared normal. Moreover, Annexin-V/propidium iodide-positive cells were observed at the perihaematomal area at 3 and 7 days implying that the neurons likely die via apoptosis. It was concluded that a population of potentially salvageable neurons exist in the perihaematomal area after cerebellar haemorrhage throughout a wide time window that could be amenable to treatment. PMID:27327104

  19. Regional cerebral glucose metabolism associated with ataxic gait. An FDG-PET activation study in patients with olivo-pontocerebellar atrophy

    In 7 patients with olivo-pontocerebellar atrophy (OPCA), regional cerebral glucose metabolism was evaluated using 18F-FDG PET under two different conditions; 30 minutes' treadmill walking, and supine resting. The two sets of PET images were three-dimensionally registered to the MRI. Then, the PET images were normalized by the global value. Regions of interest (ROIs) were drawn on the cerebellar vermis, cerebellar hemispheres, pons, and thalamus, and FDG uptake was obtained to calculate the activation ratio (=[FDG uptake under walking]/ [FDG uptake under resting]) for each region. Normalized resting FDG uptake had no significant difference between controls and OPCA patients in any region. Activation ratio of OPCA patients was significantly decreased in the cerebellar vermis compared with the controls. In the controls, FDG uptake had little difference between resting and walking in the cerebellar hemisphere, pons and thalamus. On the other hand, the FDG uptake of OPCA patients was moderately increased by walking in these regions. The reduction of activation ratio in the cerebellar vermis reflects the dysfunction caused by degeneration. The result suggests that the PET activation study can demonstrate cerebellar dysfunction in the early phase of OPCA, in which other neuro-imaging methods cannot detect the tissue atrophy, hypometabolism or hypoperfusion in the resting state. In the cerebellar hemisphere, pons and thalamus, the activation ratio was nearly equal to one in control subjects, while it was larger in OPCA patients. The instability during the ataxic gait increases the inputs from the vestibular, somatosensory and visual systems to these regions and outputs from these regions to the other neural systems. In conclusion, PET activation study is a useful and noninvasive technique for investigating the brain function associated with human gait. (H.O.)

  20. Neurotrophic effects of a cyanine dye via the PI3K-Akt pathway: attenuation of motor discoordination and neurodegeneration in an ataxic animal model.

    Hitomi Ohta

    Full Text Available BACKGROUND: Neurotrophic factors may be future therapeutic agents for neurodegenerative disease. In the screening of biologically active molecules for neurotrophic potency, we found that a photosensitizing cyanine dye, NK-4, had remarkable neurotrophic activities and was a potent radical scavenger. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we evaluated the effect of NK-4 on the protection of neurons against oxidative damage and investigated the associated intracellular signaling pathways. Subsequently, we evaluated the effect of NK-4 in an animal model of neurodegeneration. In vitro, NK-4 showed dose-dependent protection of PC12 cells from toxicity induced by oxidative stress caused by hydrogen peroxide (H(2O(2 or 6-hydroxydopamine (6-OHDA. Comparison of extracellular signal-regulated kinase signaling pathways between treatment with NK-4 and nerve growth factor (NGF using K252a, an inhibitor of the NGF receptor TrkA, revealed that NK-4 activity occurs independently of NGF receptors. LY294002, a phosphatidylinositol 3-kinase (PI3K inhibitor, blocked the protective effect of NK-4, and NK-4 caused activation of Akt/protein kinase B, a downstream effector of PI3K. These results suggest that the neuroprotective effects of NK-4 are mediated by the PI3K-Akt signaling pathway. NK-4 treatment also attenuated stress-induced activation of SAPK/JNK, which suggests that NK-4 activates a survival signaling pathway and inhibits stress-activated apoptotic pathways independently of the TrkA receptor in neuronal cells. In vivo, administration of NK-4 improved motor coordination in genetic ataxic hamsters, as assessed by rota-rod testing. Histological analysis showed that cerebellar atrophy was significantly attenuated by NK-4 treatment. Notably, the Purkinje cell count in the treated group was threefold higher than that in the vehicle group. CONCLUSIONS/SIGNIFICANCE: These results suggest that NK-4 is a potential agent for therapy for neurodegenerative

  1. 4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6.

    Jayabal, Sriram; Chang, Hui Ho Vanessa; Cullen, Kathleen E; Watt, Alanna J


    Spinocerebellar ataxia type 6 (SCA6) is a devastating midlife-onset autosomal dominant motor control disease with no known treatment. Using a hyper-expanded polyglutamine (84Q) knock-in mouse, we found that cerebellar Purkinje cell firing precision was degraded in heterozygous (SCA6(84Q/+)) mice at 19 months when motor deficits are observed. Similar alterations in firing precision and motor control were observed at disease onset at 7 months in homozygous (SCA6(84Q/84Q)) mice, as well as a reduction in firing rate. We further found that chronic administration of the FDA-approved drug 4-aminopyridine (4-AP), which targets potassium channels, alleviated motor coordination deficits and restored cerebellar Purkinje cell firing precision to wildtype (WT) levels in SCA6(84Q/84Q) mice both in acute slices and in vivo. These results provide a novel therapeutic approach for treating ataxic symptoms associated with SCA6. PMID:27381005

  2. Mouse adhalin

    Liu, L; Vachon, P H; Kuang, W;


    analyze the biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide-specific antibodies to its cytoplasmic domain, and examined its expression and localization in vivo and in vitro. The mouse adhalin sequence was 80% identical to that of human, rabbit, and hamster. Adhalin was...... specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation in...

  3. The City Mouse and the Country Mouse


    Once two mice (老鼠) were good friends. One lived in the city, the other lived in the country (乡村). After many years, the city mouse came to see the country mouse. The country mouse took him to his house in a field. He gave him the nicest food that he could find. The city mouse said,

  4. Mouse lymphotoxin.

    Trivers, G; Braungart, D; Leonard, E J


    The addition of PHA to C3H mouse spleen cells in tissue culture led to the production of lymphotoxin (LT). Cytotoxicity was assayed by addition of the culture fluids to syngeneic target cells labeled with tritiated thymidine; after an incubation period of 72 hr the amount of radioactivity released into the supernatant was measured. The LT activity in unfractionated culture fluids survived lyophilization, remained unchanged for many weeks at 4 degrees C, and progressively decreased on heating at 56 degrees C for periods from 1 to 9 hr. Based on the G-200 Sephadex distribution coefficients for several preparations, the m.w. of mouse lymphotoxin was about 41,000 daltons. Lymphotoxin from three different spleen cell production runs was recovered from isoelectric focusing columns in sharply focused peaks, the pH of which ranged from 4.4 to 4.8. PMID:1084362

  5. Anti-inflammatory Therapy With Simvastatin Improves Neuroinflammation and CNS Function in a Mouse Model of Metachromatic Leukodystrophy.

    Stein, Axel; Stroobants, Stijn; Gieselmann, Volkmar; D'Hooge, Rudi; Matzner, Ulrich


    Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a functional deficiency of the lysosomal enzyme arylsulfatase A. The prevailing late-infantile variant of MLD is characterized by widespread and progressive demyelination of the central nervous system (CNS) causing death during childhood. In order to gain insight into the pathomechanism of the disease and to identify novel therapeutic targets, we analyzed neuroinflammation in two mouse models reproducing a mild, nondemyelinating, and a more severe, demyelinating, variant of MLD, respectively. Microgliosis and upregulation of cytokine/chemokine levels were clearly more pronounced in the demyelinating model. The analysis of the temporal cytokine/chemokine profiles revealed that the onset of demyelination is preceded by a sustained elevation of the macrophage inflammatory protein (MIP)-1α followed by an upregulation of MIP-1β, monocyte chemotactic protein (MCP)-1, and several interleukins. The tumor necrosis factor (TNF)-α remains unchanged. Treatment of the demyelinating mouse model with the nonsteroidal anti-inflammatory drug simvastatin reduced neuroinflammation, improved the swimming performance and ataxic gait, and retarded demyelination of the spinal cord. Our data suggest that neuroinflammation is causative for demyelination in MLD mice and that anti-inflammatory treatment might be a novel therapeutic option to improve the CNS function of MLD patients. PMID:25896249

  6. Physical Therapy and Rehabilitation for Ataxic Patients

    Ojoga Florina


    Full Text Available The goal of the study was to review the definition of ataxia, a movement disorder in which there is in coordination of movements and postural control, its subtypes, causes, to analyze the assessment methods in rehabilitation ant the treatment modalities from the point of view of the rehabilitation team.We observed that after a long term rehabilitation treatment, the patients with ataxia improved their balance and postural reactions, increased postural stabilization, developed new upper extremity functions and independent, functional gait.Physical therapy applications play a crucial part in the rehabilitation treatment of ataxia. Of major importance are the evaluation of the patient and the establishment of the treatment methods keeping in mind that every patient has a particular form of evolution of the disease.

  7. Gaze beats mouse

    Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin


    Facial EMG for selection is fast, easy and, combined with gaze pointing, it can provide completely hands-free interaction. In this pilot study, 5 participants performed a simple point-and-select task using mouse or gaze for pointing and a mouse button or a facial-EMG switch for selection. Gaze...... pointing was faster than mouse pointing, while maintaining a similar error rate. EMG and mouse-button selection had a comparable performance. From analyses of completion time, throughput and error rates, we concluded that the combination of gaze and facial EMG holds potential for outperforming the mouse....

  8. Intracerebroventricular enzyme infusion corrects central nervous system pathology and dysfunction in a mouse model of metachromatic leukodystrophy.

    Stroobants, Stijn; Gerlach, Debora; Matthes, Frank; Hartmann, Dieter; Fogh, Jens; Gieselmann, Volkmar; D'Hooge, Rudi; Matzner, Ulrich


    Arylsulfatase A (ASA) catalyzes the desulfation of sulfatide, a major lipid component of myelin. Inherited functional deficiencies of ASA cause the lysosomal storage disease (LSD) metachromatic leukodystrophy (MLD), which is characterized by intralysosomal accumulation of sulfatide, progressive neurological symptoms and early death. Enzyme replacement therapy (ERT) using intravenous injection of active enzyme is a treatment option for many LSDs as exogenous lysosomal enzymes are delivered to lysosomes of patient's cells via receptor-mediated endocytosis. Efficient treatment of MLD and other LSDs with central nervous system (CNS) involvement is, however, hampered by the blood-brain barrier (BBB), which limits transfer of therapeutic enzymes from the circulation to the brain parenchyma. To bypass the BBB, we infused recombinant human ASA (rhASA) by implanted miniature pumps into the cerebrospinal fluid (CSF) of a conventional and a novel, genetically aggravated ASA knockout mouse model of MLD. rhASA continuously delivered to the lateral ventricle for 4 weeks penetrated the brain parenchyma and was targeted to the lysosomes of brain cells. Histological analysis revealed complete reversal of lysosomal storage in the infused hemisphere. rhASA concentrations and sulfatide clearance declined with increasing distance from the infusion site. Correction of the ataxic gait indicated reversal of central nervous system dysfunctions. The profound histopathological and functional improvements, the requirement of low enzyme doses and the absence of immunological side effects suggest intracerebroventricular ERT to be a promising treatment option for MLD and other LSDs with prevailing CNS disease. PMID:21515587

  9. An encyclopedia of mouse DNA elements (Mouse ENCODE)

    Stamatoyannopoulos, John A; Guig?? Serra, Roderic; Djebali, Sarah; Lagarde, Julien; Adams, Leslie B.


    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  10. Mouse Phenome Database (MPD)

    U.S. Department of Health & Human Services — The Mouse Phenome Database (MPD) has characterizations of hundreds of strains of laboratory mice to facilitate translational discoveries and to assist in selection...

  11. Mouse Genome Informatics (MGI)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  12. Burn mouse models

    Calum, Henrik; Høiby, Niels; Moser, Claus


    Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third-degree b......Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third...... with infected burn wound compared with the burn wound only group. The burn mouse model resembles the clinical situation and provides an opportunity to examine or develop new strategies like new antibiotics and immune therapy, in handling burn wound victims much....

  13. Manipulation of Mouse Embryonic Stem Cells for Knockout Mouse Production

    Limaye, Advait; Hall, Bradford; Kulkarni, Ashok B.


    The establishment of mouse embryonic stem (ES) cell liness has allowed for the generation of the knockout mouse. ES cells that are genetically altered in culture can then be manipulated to derive a whole mouse containing the desired mutation. To successfully generate a knockout mouse, however, the ES cells must be carefully cultivated in a pluripotent state throughout the gene targeting experiment. This unit describes detailed step-by-step protocols, reagents, equipment, and strategies needed...

  14. Mouse Leydig Tumor Cells

    Bo-Syong Pan


    Full Text Available Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS. We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

  15. Mouse-X

    Tagg, Justin


    Mouse-X is a short Science Fiction film completed in 2014. It explores identity and reality through a powerful short story about a man trapped in a building with a thousand clones of himself, begging the question, 'Who are you, if you're not the only you?'

  16. Colonization, mouse-style

    Searle Jeremy B


    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article:

  17. Mouse genetics: Catalogue and scissors

    Han-Woong Lee


    Full Text Available Phenotypic analysis of gene-specific knockout (KO mice hasrevolutionized our understanding of in vivo gene functions. Asthe use of mouse embryonic stem (ES cells is inevitable forconventional gene targeting, the generation of knockout miceremains a very time-consuming and expensive process. Toaccelerate the large-scale production and phenotype analyses ofKO mice, international efforts have organized global consortiasuch as the International Knockout Mouse Consortium (IKMCand International Mouse Phenotype Consortium (IMPC, andthey are persistently expanding the KO mouse catalogue that ispublicly available for the researches studying specific genes ofinterests in vivo. However, new technologies, adoptingzinc-finger nucleases (ZFNs or Transcription Activator-LikeEffector (TALE Nucleases (TALENs to edit the mouse genome,are now emerging as valuable and effective shortcuts alternativefor the conventional gene targeting using ES cells. Here, weintroduce the recent achievement of IKMC, and evaluate thesignificance of ZFN/TALEN technology in mouse genetics.

  18. Mouse models of colorectal cancer

    Yunguang Tong; Wancai Yang; H. Phillip Koeffler


    Colorectal cancer is one of the most common malignancies in the world. Many mouse models have been developed to evaluate features of colorectal cancer in humans. These can be grouped into genetically-engineered, chemically-induced, and inoculated models. However, none recapitulates all of the characteristics of human colorectal cancer. It is critical to use a specific mouse model to address a particular research question. Here, we review commonly used mouse models for human colorectal cancer.

  19. Multimodal photoacoustic ophthalmoscopy in mouse

    Song, Wei; Wei, Qing; Feng, Liang; Sarthy, Vijay; Jiao, Shuliang; LIU, XIAORONG; Zhang, Hao F.


    Photoacoustic ophthalmoscopy (PAOM) is a novel imaging technology that measures optical absorption in the retina. The capability of PAOM can be further enhanced if it could image mouse eyes, because mouse models are widely used for various retinal diseases. The challenges in achieving high-quality imaging of mouse retina, however, come from the much smaller eyeball size. Here, we report an optimized imaging system, which integrates PAOM, spectral-domain optical coherence tomography (SD-OCT), ...

  20. Mouse models of medulloblastoma

    Xiaochong Wu; Paul A. Northcott; Sidney Croul; Michael D. Taylor


    Medulloblastoma is the most common malignant pediatric brain tumor. Despite its prevalence and importance in pediatric neuro-oncology, the genes and pathways responsible for its initiation, maintenance,and progression remain poorly understood. Genetically engineered mouse models are an essential tool for uncovering the molecular and cellular basis of human diseases, including cancer, and serve a valuable role as preclinical models for testing targeted therapies. In this review, we summarize how such models have been successfully applied to the study of medulloblastoma over the past decade and what we might expect in the coming years.

  1. MouseCyc: a curated biochemical pathways database for the laboratory mouse

    Evsikov, Alexei V.; Dolan, Mary E; Genrich, Michael P; Patek, Emily; Bult, Carol J


    Linking biochemical genetic data to the reference genome for the laboratory mouse is important for comparative physiology and for developing mouse models of human biology and disease. We describe here a new database of curated metabolic pathways for the laboratory mouse called MouseCyc . MouseCyc has been integrated with genetic and genomic data for the laboratory mouse available from the Mouse Genome Informatics database and with pathway data from other organisms, including human.

  2. Speech Motor Programming in Hypokinetic and Ataxic Dysarthria

    Spencer, K.A.; Rogers, M.A.


    It is widely accepted that the cerebellar and basal ganglia control circuits contribute to the programming of movement. Converging evidence from neuroimaging, limb control, and neuropsychological studies suggests that (1) people with cerebellar disease have reduced ability to program movement sequences in advance of movement onset and (2) people…

  3. Whole mouse cryo-imaging

    Wilson, David; Roy, Debashish; Steyer, Grant; Gargesha, Madhusudhana; Stone, Meredith; McKinley, Eliot


    The Case cryo-imaging system is a section and image system which allows one to acquire micron-scale, information rich, whole mouse color bright field and molecular fluorescence images of an entire mouse. Cryo-imaging is used in a variety of applications, including mouse and embryo anatomical phenotyping, drug delivery, imaging agents, metastastic cancer, stem cells, and very high resolution vascular imaging, among many. Cryo-imaging fills the gap between whole animal in vivo imaging and histology, allowing one to image a mouse along the continuum from the mouse -> organ -> tissue structure -> cell -> sub-cellular domains. In this overview, we describe the technology and a variety of exciting applications. Enhancements to the system now enable tiled acquisition of high resolution images to cover an entire mouse. High resolution fluorescence imaging, aided by a novel subtraction processing algorithm to remove sub-surface fluorescence, makes it possible to detect fluorescently-labeled single cells. Multi-modality experiments in Magnetic Resonance Imaging and Cryo-imaging of a whole mouse demonstrate superior resolution of cryo-images and efficiency of registration techniques. The 3D results demonstrate the novel true-color volume visualization tools we have developed and the inherent advantage of cryo-imaging in providing unlimited depth of field and spatial resolution. The recent results continue to demonstrate the value cryo-imaging provides in the field of small animal imaging research.


    Apoptosis in Whole Mouse Ovaries Robert M. Zucker Susan C. Jeffay and Sally D. Perreault Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711.

  5. Mouse models for cancer research

    Wei Zhang; Lynette Moore; Ping Ji


    Mouse models of cancer enable researchers to leamn about tumor biology in complicated and dynamic physiological systems. Since the development of gene targeting in mice, cancer biologists have been among the most frequent users of transgenic mouse models, which have dramatically increased knowledge about how cancers form and grow. The Chinese Joumnal of Cancer will publish a series of papers reporting the use of mouse models in studying genetic events in cancer cases. This editorial is an overview of the development and applications of mouse models of cancer and directs the reader to upcoming papers describing the use of these models to be published in coming issues, beginning with three articles in the current issue.

  6. Hand gestures mouse cursor control

    Marian-Avram Vincze


    Full Text Available The paper describes the implementation of a human-computer interface for controlling the mouse cursor. The test reveal the fact: a low-cost web camera some processing algorithms are quite enough to control the mouse cursor on computers. Even if the system is influenced by the illuminance level on the plane of the hand, the current study may represent a start point for some studies on the hand tracking and gesture recognition field.

  7. Mouse meninges isolation for FACS



    Authors: Noel Derecki & Jonathan Kipnis ### Abstract Presented is a method for removal of meninges from the brain and interior skull of the mouse yielding tissue suitable for preparing a single-cell suspension amenable to downstream applications such as flow cytometric analysis or short-term cell culture. ### Materials 1. Nembutal (or similar, as approved by your governing body) - Perfusion apparatus suitable for transcardial mouse perfusion - Perfusion Buffer (0.1M...

  8. 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.)

  9. 10. international mouse genome conference

    Meisler, M.H.


    Ten years after hosting the First International Mammalian Genome Conference in Paris in 1986, Dr. Jean-Louis Guenet presided over the Tenth Conference at the Pasteur Institute, October 7--10, 1996. The 1986 conference was a satellite to the Human Gene Mapping Workshop and had approximately 50 attendees. The 1996 meeting was attended by 300 scientists from around the world. In the interim, the number of mapped loci in the mouse increased from 1,000 to over 20,000. This report contains a listing of the program and its participants, and two articles that review the meeting and the role of the laboratory mouse in the Human Genome project. More than 200 papers were presented at the conference covering the following topics: International mouse chromosome committee meetings; Mutant generation and identification; Physical and genetic maps; New technology and resources; Chromatin structure and gene regulation; Rate and hamster genetic maps; Informatics and databases; and Quantitative trait analysis.

  10. Mouse models of Fanconi anemia

    Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.

  11. Gesture Recognition Based Mouse Events

    Rachit Puri


    Full Text Available This paper presents the maneuver of mouse pointer a nd performs various mouse operations such as left click, right click, double click, drag etc using ge stures recognition technique. Recognizing gestures is a complex task which involves many aspects such as mo tion modeling, motion analysis, pattern recognition and machine learning. Keeping all the essential factors in mind a system has been created which recognizes the movement of fingers and various patterns formed by them. Color caps have been used for fingers to distinguish it f rom the background color such as skin color. Thus recog nizing the gestures various mouse events have been performed. The application has been created on MATL AB environment with operating system as windows 7.

  12. Mouse models of Fanconi anemia

    Parmar, Kalindi; D' Andrea, Alan [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Niedernhofer, Laura J., E-mail: [Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine and Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center, Research Pavilion 2.6, Pittsburgh, PA 15213-1863 (United States)


    Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.

  13. Mouse Stirs up Breast Cancer

    Helen Pilcher; 孙雯


    @@ The humble house mouse could be more dangerous than we thought,according to a study that suggests a rodent① virus plays a role in the development of breast cancer. But the finding is contentious② and reignites③ a long-standing④wrangle⑤ about the potential⑥ causes of the disease.

  14. Mouse Models of Rheumatoid Arthritis.

    Caplazi, P; Baca, M; Barck, K; Carano, R A D; DeVoss, J; Lee, W P; Bolon, B; Diehl, L


    Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients. PMID:26063174

  15. The Mouse SAGE Site: database of public mouse SAGE libraries

    Divina, Petr; Forejt, Jiří


    Roč. 32, - (2004), s. D482-D483. ISSN 0305-1048 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015 Grant ostatní: HHMI(US) 555000306 Institutional research plan: CEZ:AV0Z5052915 Keywords : mouse SAGE libraries * web-based database Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.260, year: 2004

  16. Element profiles of mouse hair

    Element profile patterns of growth and nongrowth phase hair were obtained for the C57L/J male mouse using a proton microprobe. Growth phase hair profiles of Cl, S, K and P show that these elements are concentrating in regions of higher pigmentation. Calcium is restricted to the medulla region in the hair shaft. For nongrowth phase hair, the profiles of Cl and S are essentially unchanged, whereas K and P are depleted in the hair shaft and are concentrating in the cornified root sheath. The element patterns found for the nongrowth phase profiles of mouse hair show striking similarities to previously reported patterns for growth profiles of human hair. (author) 10 refs.; 4 figs

  17. Mouse models for colorectal cancer

    KARIM, BAKTIAR O.; Huso, David L.


    Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States, with the number of affected people increasing. There are many risk factors that increase CRC risk, including family or personal history of CRC, smoking, consumption of red meat, obesity, and alcohol consumption. Conversely, increased screening, maintaining healthy body weight, not smoking, and limiting intake of red meat are all associated with reduced CRC morbidity and mortality. Mouse models of ...

  18. Therapeutic cloning in the mouse

    Mombaerts, Peter


    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of d...

  19. Mouse models for human diseases

    Lee, AYW; Chung, SK; Chung, SSM


    Mice are increasingly being used as models for the study of various human diseases. This is primarily because among mammalian modals, they are most amenable to genetic manipulations. As we attempt to understand the molecular mechanism of diseases, it is imperative that the genes involved in the disease process be identified. One approach is to study mouse mutants with symptoms analogous to human diseases, and try to identify the genes responsible. Another approach is to manipulate the express...

  20. Mouse models for methylmalonic aciduria.

    Heidi L Peters

    Full Text Available Methylmalonic aciduria (MMA is a disorder of organic acid metabolism resulting from a functional defect of methylmalonyl-CoA mutase (MCM. MMA is associated with significant morbidity and mortality, thus therapies are necessary to help improve quality of life and prevent renal and neurological complications. Transgenic mice carrying an intact human MCM locus have been produced. Four separate transgenic lines were established and characterised as carrying two, four, five or six copies of the transgene in a single integration site. Transgenic mice from the 2-copy line were crossed with heterozygous knockout MCM mice to generate mice hemizygous for the human transgene on a homozygous knockout background. Partial rescue of the uniform neonatal lethality seen in homozygous knockout mice was observed. These rescued mice were significantly smaller than control littermates (mice with mouse MCM gene. Biochemically, these partial rescue mice exhibited elevated methylmalonic acid levels in urine, plasma, kidney, liver and brain tissue. Acylcarnitine analysis of blood spots revealed elevated propionylcarnitine levels. Analysis of mRNA expression confirms the human transgene is expressed at higher levels than observed for the wild type, with highest expression in the kidney followed closely by brain and liver. Partial rescue mouse fibroblast cultures had only 20% of the wild type MCM enzyme activity. It is anticipated that this humanised partial rescue mouse model of MMA will enable evaluation of long-term pathophysiological effects of elevated methylmalonic acid levels and be a valuable model for the investigation of therapeutic strategies, such as cell transplantation.

  1. Mouse Models of Bone Marrow Transplantation

    Reddy, Pavan; Negrin, Robert; Hill, Geoffrey R.


    Over the last 50 years, mouse models of bone marrow transplantation have provided the critical links between graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) pathophysiology and clinical practice. The initial insight from mouse models that GVHD and GVL were T cell dependent has long been confirmed clinically. More recent translations from mouse models have included the important role of inflammatory cytokines in GVHD. Newly developed concepts relating to the ability of antigen...

  2. Mouse Models of Williams-Beuren Syndrome

    Osborne, L.R.


    In an attempt to dissect the contribution of individual genes to the complex and varied phenotype associated with Williams-Beuren syndrome (WBS), researchers have turned to mouse models. The mouse genome is easily manipulated to produce animals that are genetic copies of humans with genetic conditions, be it with null mutations, hypomorphic mutations, point mutations or even large deletions encompassing many genes. Over the past few years, several mouse models knocking out genes f...

  3. The Mouse Genome Database (MGD): expanding genetic and genomic resources for the laboratory mouse

    Blake, Judith A.; Eppig, Janan T.; Richardson, Joel E.; Davisson, Muriel T.; the Mouse Genome Database Group,


    The Mouse Genome Database (MGD) is a comprehensive public database of mouse genomic, genetic and phenotypic information ( ). This community database provides information about genes, serves as a mapping resource of the mouse genome, details mammalian orthologs, integrates experimental data, represents standardized mouse nomenclature for genes and alleles, incorporates links to other genomic resources such as sequence data, and includes a variety of additional inf...

  4. The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping

    Steve D M Brown; Moore, Mark W.


    Determining the function of all mammalian genes remains a major challenge for the biomedical science community in the 21st century. The goal of the International Mouse Phenotyping Consortium (IMPC) over the next 10 years is to undertake broad-based phenotyping of 20,000 mouse genes, providing an unprecedented insight into mammalian gene function. This short article explores the drivers for large-scale mouse phenotyping and provides an overview of the aims and processes involved in IMPC mouse ...

  5. Steroid metabolism in the mouse placenta

    The purpose of the study described in this thesis was to investigate the capacity for steroid synthesis of the mouse placenta - especially the production of progesterone, androgens and estrogens - and to determine, if possible, the relation of steroid synthesis to special cell types. In an introductory chapter the androgen production in the mouse placenta is surveyed by means of a histochemical and bioindicator study of different stages of development of the placenta. The metabolism of [3H]-dehydroepiandrosterone and [3H]-progesterone by mouse placental tissue in vitro is studied. The metabolism of [3H]-progesterone by the mouse fetal adrenal in vitro is also studied

  6. Mouse mammary tumor biology: a short history.

    Cardiff, Robert D; Kenney, Nicholas


    For over a century, mouse mammary tumor biology and the associated Mouse mammary tumor virus (MMTV) have served as the foundation for experimental cancer research, in general, and, in particular, experimental breast cancer research. Spontaneous mouse mammary tumors were the basis for studies of the natural history of neoplasia, oncogenic viruses, host responses, endocrinology, and neoplastic progression. However, lacking formal proof of a human mammary tumor virus, the preeminence of the mouse model faded in the 1980s. Since the late 1980s, genetically engineered mice (GEM) have proven extremely useful for studying breast cancer and have become the animal model for human breast cancer. Hundreds of mouse models of human breast cancer have been developed since the first demonstration, in 1984, that the mouse mammary gland could be molecularly targeted and used to test the oncogenicity of candidate human genes. Now, very few scientists can avoid using a mouse model to test the biology of their favorite gene. The GEM have attracted a new generation of molecular and cellular biologists eager to apply their skills to these surrogates of the human disease. Newcomers often enter the field without an appreciation of the origins of mouse mammary tumor biology and the basis for many of the prevailing concepts. Our purpose in writing this short history of mouse mammary tumor biology is to provide a historical perspective for the benefit of the newcomers. If Einstein was correct in that "we stand on the shoulders of giants," the neophytes should meet their giants. PMID:17433908

  7. Mouse models of pancreatic cancer

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda


    Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are lacking.Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed.In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes.In the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed.These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer.Genetic alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice.These mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system.These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer treatments.Here,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

  8. Take care of your mouse!

    IT Department


    “Stop --- Think --- Click" is the basic recommendation for securely browsing the Internet and for securely reading e-mails. Users who have followed this recommendation in the past were less likely to have their computer infected or their computing account compromised. We would like to thank all those who donated their mouse to the CERN Animal Shelter for Computer Mice ( For those who still use a mouse, please stay vigilant and  alert: do not click on links whose origin you do not trust or which look like gibberish. Do not install untrusted software or plug-ins, since software from untrusted sources may infect or compromise your computer, or violate copyrights. Finally, take particular care with e-mails: Do not open unexpected or suspicious e-mails or attachments. Delete them if they do not concern you or if they appear strange. If in doubt, or if you have questions, please do not hesitate to contact

  9. Mouse Models of Tumor Immunotherapy.

    Ngiow, Shin Foong; Loi, Sherene; Thomas, David; Smyth, Mark J


    Immunotherapy is now evolving into a major therapeutic option for cancer patients. Such clinical advances also promote massive interest in the search for novel immunotherapy targets, and to understand the mechanism of action of current drugs. It is projected that a series of novel immunotherapy agents will be developed and assessed for their therapeutic activity. In light of this, in vivo experimental mouse models that recapitulate human malignancies serve as valuable tools to validate the efficacy and safety profile of immunotherapy agents, before their transition into clinical trials. In this review, we will discuss the major classes of experimental mouse models of cancer commonly used for immunotherapy assessment and provide examples to guide the selection of appropriate models. We present some new data concerning the utility of a carcinogen-induced tumor model for comparing immunotherapies and combining immunotherapy with chemotherapy. We will also highlight some recent advances in experimental modeling of human malignancies in mice that are leading towards personalized therapy in patients. PMID:26922998

  10. Mouse models of congenital cataract.

    Graw, J


    Mouse mutants affecting lens development are excellent models for corresponding human disorders. The mutant aphakia has been characterised by bilaterally aphakic eyes (Varnum and Stevens, J Hered 1968;59:147-50); the corresponding gene was mapped to chromosome 19 (Varnum and Stevens, Mouse News Lett 1975;53:35). Recent investigations in our laboratory refined the linkage of 0.6 cM proximal to the marker D19Mit10. Several candidate genes have been excluded (Chuk1, Fgf8, Lbp1, Npm3, Pax2, Pitx3). The Cat3 mutations are characterised by vacuolated lenses caused by alterations in the initial secondary lens fibre cell differentiation. Secondary malformations develop at the cornea and iris, but the retina remains unaffected. The mutation has been mapped to chromosome 10 close to the markers D10Mit41 and D10Mit95. Several candidate genes have been excluded (Dcn, Elk3, Ldc, Mell8, Tr2-11). The series of Cat2 mutations have been mapped close to the gamma-crystallin genes (Cryg; Löster et al., Genomics 1994;23:240-2). The Cat2nop mutation is characterised by a mutation in the third exon of Crygb leading to a truncated gamma B-crystallin and the termination of lens fibre cell differentiation. The Cat2 mutants are interesting models for human cataracts caused by mutations in the human CRYG genes at chromosome 2q32-35. PMID:10627821

  11. The chromosomal location of mouse interferon alpha genes.

    Lovett, M; Cox, D. R.; Yee, D; Boll, W; Weissmann, C; Epstein, C J; Epstein, L B


    The chromosomal location of mouse leukocyte-interferon (IFN-alpha) genes was determined by Southern blot analysis of DNA from a panel of Chinese hamster x mouse somatic cell hybrids using a mouse IFN-alpha cDNA as a hybridization probe. All resolvable mouse genes are located on mouse chromosome 4. In addition, two common restriction site polymorphisms within these genes were identified in several mouse strains.

  12. Mouse adenovirus type 1 infection of macrophages

    Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.


    Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.

  13. A catalog of the mouse gut metagenome

    Xiao, Liang; Feng, Qiang; Liang, Suisha;


    We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laborato......We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing...... laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human...

  14. Optimization of the virtual mouse HeadMouse to foster its classroom use by children with physical disabilities

    Merce TEIXIDO; Tomás PALLEJA; Tresanchez, Marcel; Font, Davinia; Moreno, Javier; Fernández, Alicia; PALACÍN, JORDI; Rebate, Carlos


    This paper presents the optimization of a virtual mouse called HeadMouse in order to foster its classroom use by children with physical disabilities. HeadMouse is an absolute virtual mouse that converts head movements in cursor displacement and facial gestures in click actions. The virtual mouse combines different image processing algorithms: face detection, pattern matching and optical flow in order to emulate the behaviour of a conventional computer mouse. The original implementation of Hea...

  15. The International Mouse Strain Resource (IMSR): cataloging worldwide mouse and ES cell line resources.

    Eppig, Janan T; Motenko, Howie; Richardson, Joel E; Richards-Smith, Beverly; Smith, Cynthia L


    The availability of and access to quality genetically defined, health-status known mouse resources is critical for biomedical research. By ensuring that mice used in research experiments are biologically, genetically, and health-status equivalent, we enable knowledge transfer, hypothesis building based on multiple data streams, and experimental reproducibility based on common mouse resources (reagents). Major repositories for mouse resources have developed over time and each has significant unique resources to offer. Here we (a) describe The International Mouse Strain Resource that offers users a combined catalog of worldwide mouse resources (live, cryopreserved, embryonic stem cells), with direct access to repository sites holding resources of interest and (b) discuss the commitment to nomenclature standards among resources that remain a challenge in unifying mouse resource catalogs. PMID:26373861

  16. Optimizing mouse models for precision cancer prevention.

    Le Magnen, Clémentine; Dutta, Aditya; Abate-Shen, Cory


    As cancer has become increasingly prevalent, cancer prevention research has evolved towards placing a greater emphasis on reducing cancer deaths and minimizing the adverse consequences of having cancer. 'Precision cancer prevention' takes into account the collaboration of intrinsic and extrinsic factors in influencing cancer incidence and aggressiveness in the context of the individual, as well as recognizing that such knowledge can improve early detection and enable more accurate discrimination of cancerous lesions. However, mouse models, and particularly genetically engineered mouse (GEM) models, have yet to be fully integrated into prevention research. In this Opinion article, we discuss opportunities and challenges for precision mouse modelling, including the essential criteria of mouse models for prevention research, representative success stories and opportunities for more refined analyses in future studies. PMID:26893066

  17. Mouse Adenovirus Type 1 Infection of Macrophages

    Ashley, Shanna L.; Welton, Amanda R.; Harwood, Kirsten M.; van Rooijen, Nico; Spindler, Katherine R.


    Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus. Here we determined the extent and functional importance of macrophage infection by MAV-1. Bone marrow-derived macrophages expressed MAV-1 mRNAs and proteins upon ex vivo infection. Adherent perito...

  18. FACS of acutely isolated mouse microglia



    Authors: Noel Derecki, James Cronk & Jonathan Kipnis ### Abstract Here, we describe a protocol in which single cells are isolated acutely from adult mouse brains, made into single cell suspensions, depleted of myelin debris, then stained for markers to determine microglial contents. Cells are fixed and read on a multicolor flow cytometer. ### Procedure 1. Perfuse mouse thoroughly transcardially with pH 7.4 0.1M PBS - Remove heads with scissors. - Strip skulls of soft...

  19. Special nutrition in mouse developmental oocytes

    Yu, Ling; Wang, Shu-Fang; Yao, Yuan-qing


    Investigation of nutrition-related proteins in mouse oocytes and zygotes is crucial for the development of an effective therapy for patients with infertility. Currently, we are concerned with the role of nutrition in the process of oocyte development in order to better reveal the relationship between nutrition and infertility. We collected mouse oocytes at three different developmental stages: germinal vesicle (GV) stage, metaphase II-arrested (MII) stage and fertilized oocytes (zygotes). Sem...

  20. A Color Based Touchless Finger Mouse

    Kah-Meng Kwong; Chin-Poo Lee; Kian-Ming Lim; Siew-Chin Chong; Siti Fatimah Abdul Razak


    People work with computers almost anytime, everywhere  in the current trend. However, continuously controlling a computer with mouse for a long time might cause much strains to people’s wrist. This work proposes a touchless finger mouse using webcam. A marker with different colours representing different actions is used. The webcam will capture the information on the marker and trigger the associated actions. This prototype is proven to be able to perform most of the actions a normal mouser c...

  1. Development of Orthotopic Pancreatic Tumor Mouse Models

    Qiu, Wanglong; Gloria H. Su


    Genetically engineered mouse models of pancreatic cancer that recapitulate human pancreatic tumorigenesis have been established. However, the cost associated with generating and housing these mice can be prohibitive. Tumor latency and progression to invasive diseases in these models are also highly variable. Xenograft mouse models of human pancreatic cancer including heterotopic and orthotopic have been widely used in preclinical studies for their comparatively low cost and rapid, predictable...

  2. Connexins and steroidogenesis in mouse Leydig cells

    Li, Dan; Sekhon, Poonam; Barr, Kevin J.; Márquez-Rosado, Lucrecia; Lampe, Paul D; Kidder, Gerald M.


    Connexin43 has been recognized as forming gap junctions in Leydig cells. However, previous work had shown that mouse Leydig cells lacking this connexin do not suffer any limitation of their ability to produce testosterone when stimulated with luteinizing hormone. The objective of the present study was to identify additional connexins in mouse Leydig cells that could be required for steroidogenesis. An RT-PCR screen involving isolated adult Leydig cells identified connexin36 and connexin45 as ...

  3. The wobbler mouse, an ALS animal model

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas


    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking similarities to ALS. The cellular effects of the wobbler mutation, cellular transport defects, neurofilament aggregation, neuronal hyperexcitability and neuroinflammation closely resemble human ALS. Now,...

  4. Optical mouse acting as biospeckle sensor

    da Silva, Michel Melo; Nozela, Jose Roberto de Almeida; Chaves, Marcio Jose; Alves Braga, Roberto; Rabal, Hector Jorge


    In this work we propose some experiments with the use of optical computer mouse, associated to low cost lasers that can be used to perform several measurements with applications in industry and in human health monitoring. The mouse was used to grab the movements produced by speckle pattern changes and to get information through the adaptation of its structure. We measured displacements in wood samples under strain, variations of the diameter of an artery due to heart beat and, through a hardware simulation, the movement of an eye, an experiment that could be of low cost help for communication to severely handicapped motor patients. Those measurements were done in spite of the fact that the CCD sensor of the mice is monolithically included into an integrated circuit so that the raw image cannot be accessed. If, as was the case with primitive optical mouse, that signal could be accessed, the quality and usefulness of the measurements could be significantly increased. As it was not possible, a webcam sensor was used for measuring the drying of paint, a standard phenomenon for testing biospeckle techniques, in order to prove the usefulness of the mouse design. The results showed that the use of the mouse associated to a laser pointer could be the way to get metrological information from many phenomena involving the whole field spatial displacement, as well as the use of the mouse as in its prime version allowed to get images of the speckle patterns and to analyze them.

  5. Mouse Models for Filovirus Infections

    Kelly L. Warfield


    Full Text Available The filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (HF in humans and nonhuman primates. Because many cases have occurred in geographical areas lacking a medical research infrastructure, most studies of the pathogenesis of filoviral HF, and all efforts to develop drugs and vaccines, have been carried out in biocontainment laboratories in non-endemic countries, using nonhuman primates (NHPs, guinea pigs and mice as animal models. NHPs appear to closely mirror filoviral HF in humans (based on limited clinical data, but only small numbers may be used in carefully regulated experiments; much research is therefore done in rodents. Because of their availability in large numbers and the existence of a wealth of reagents for biochemical and immunological testing, mice have become the preferred small animal model for filovirus research. Since the first experiments following the initial 1967 marburgvirus outbreak, wild-type or mouse-adapted viruses have been tested in immunocompetent or immunodeficient mice. In this paper, we review how these types of studies have been used to investigate the pathogenesis of filoviral disease, identify immune responses to infection and evaluate antiviral drugs and vaccines. We also discuss the strengths and weaknesses of murine models for filovirus research, and identify important questions for further study.

  6. Ethical Considerations in Mouse Experiments.

    Baertschi, Bernard; Gyger, Marcel


    Mice count morally because they can be harmed. This raises a moral issue in animal experimentation. Three main ethical attitudes towards animals are reviewed here. The Kantian view denies moral value to animals because they lack reason. The second view, by Singer, considers animals as sentient creatures (i.e., able to suffer). Finally, Regan considers that animals are subjects of their own life; they are autonomous and therefore have moral rights. Singer is a reformist and allows animal experimentation under certain conditions. Regan is abolitionist, saying that animals have moral rights that cannot be negotiated. Current animal protection legislation strives to put in balance the human and animal interests to decide whether an animal experiment is morally justified or not. An ethical evaluation process is conducted based on the harm-benefit assessment of the experiment. The researcher has to implement the 3Rs (Replacement, Reduction, Refinement) to minimize the harms to the animals and make sure that the outcomes are scientifically significant and that the quality of the science is high, in order to maximize benefits to humans and animals. Curr. Protoc. Mouse Biol. 1:155-167. © 2011 by John Wiley & Sons, Inc. PMID:26068990

  7. Pathology of Mouse Models of Accelerated Aging.

    Harkema, L; Youssef, S A; de Bruin, A


    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience," which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging. This review provides an overview of the most commonly reported nonneoplastic macroscopic and microscopic pathologic findings in progeroid mouse models (eg, osteoporosis, osteoarthritis, degenerative joint disease, intervertebral disc degeneration, kyphosis, sarcopenia, cutaneous atrophy, wound healing, hair loss, alopecia, lymphoid atrophy, cataract, corneal endothelial dystrophy, retinal degenerative diseases, and vascular remodeling). Furthermore, several shortcomings in pathologic analysis and descriptions of these models are discussed. Progeroid mouse models are valuable models for aging, but thorough knowledge of both the mouse strain background and the progeria-related phenotype is required to guide interpretation and translation of the pathology data. PMID:26864891

  8. Mouse Simulation Using Two Coloured Tapes

    Kumar, Vikram; Mahe, Swapnil; Vyawahare, Swapnil; 10.5121/ijist.2012.2206


    In this paper, we present a novel approach for Human Computer Interaction (HCI) where, we control cursor movement using a real-time camera. Current methods involve changing mouse parts such as adding more buttons or changing the position of the tracking ball. Instead, our method is to use a camera and computer vision technology, such as image segmentation and gesture recognition, to control mouse tasks (left and right clicking, double-clicking, and scrolling) and we show how it can perform everything as current mouse devices can. The software will be developed in JAVA language. Recognition and pose estimation in this system are user independent and robust as we will be using colour tapes on our finger to perform actions. The software can be used as an intuitive input interface to applications that require multi-dimensional control e.g. computer games etc.

  9. Measuring Pressure Volume Loops in the Mouse.

    Townsend, DeWayne


    Understanding the causes and progression of heart disease presents a significant challenge to the biomedical community. The genetic flexibility of the mouse provides great potential to explore cardiac function at the molecular level. The mouse's small size does present some challenges in regards to performing detailed cardiac phenotyping. Miniaturization and other advancements in technology have made many methods of cardiac assessment possible in the mouse. Of these, the simultaneous collection of pressure and volume data provides a detailed picture of cardiac function that is not available through any other modality. Here a detailed procedure for the collection of pressure-volume loop data is described. Included is a discussion of the principles underlying the measurements and the potential sources of error. Anesthetic management and surgical approaches are discussed in great detail as they are both critical to obtaining high quality hemodynamic measurements. The principles of hemodynamic protocol development and relevant aspects of data analysis are also addressed. PMID:27166576

  10. OCT guided microinjections for mouse embryonic research

    Larin, Kirill V.; Syed, Saba H.; Coughlin, Andrew J.; Wang, Shang; West, Jennifer L.; Dickinson, Mary E.; Larina, Irina V.


    Optical coherence tomography (OCT) is gaining popularity as live imaging tool for embryonic research in animal models. Recently we have demonstrated that OCT can be used for live imaging of cultured early mouse embryos (E7.5-E10) as well as later stage mouse embryos in utero (E12.5 to the end of gestation). Targeted delivery of signaling molecules, drugs, and cells is a powerful approach to study normal and abnormal development, and image guidance is highly important for such manipulations. Here we demonstrate that OCT can be used to guide microinjections of gold nanoshell suspensions in live mouse embryos. This approach can potentially be used for variety of applications such as guided injections of contrast agents, signaling molecules, pharmacological agents, cell transplantation and extraction, as well as other image-guided micromanipulations. Our studies also reveal novel potential for gold nanoshells in embryonic research.

  11. Sphingolipid metabolism in organotypic mouse keratinocyte cultures

    Ceramides are the dominant component of the stratum corneum intercellular lipid lamellae, which constitute the epidermal permeability barrier. Only pig and human epidermal ceramides have been extensively characterized and the structures of the ceramides of cultured keratinocytes have not been previously investigated. In the present studies, we have characterized the ceramides synthesized by organotypic lifted mouse keratinocyte cultures for the first time and compared them to the ceramides of intact mouse epidermis. Both mouse epidermis and cultures contained five ceramides, ceramide 1 being the least polar and ceramide 5 the most polar. Ceramide 1 was a group of acylceramides, i.e., very-long-chain omega-hydroxyceramides with an ester-linked nonhydroxy fatty acid. Ceramide 2 contained medium-length saturated nonhydroxy fatty acids. (In culture, the ceramide 2 band was split into two parts with the slightly more polar ceramide 2' containing short-chain saturated nonhydroxy fatty acids.) Ceramide 5 contained short-chain alpha-hydroxy fatty acids. The structures of ceramides 1, 2, and 5 were analagous to those of pig and human epidermis. Mouse epidermal ceramide 3 was quite unusual, containing beta-hydroxy fatty acids, a structure not previously identified among mammalian ceramides. In contrast, culture ceramide 3 was composed of omega-hydroxy fatty acids with a chain-length distribution similar to that of ceramide 1. Mouse ceramide 4 was composed of fatty acids with chromatographic mobility similar to hydroxy fatty acids but with different chemical reactivity; it remains only partially characterized. Culture ceramide 4 was present in quantities too small for analysis. All ceramides in mouse epidermis and cultures contained only sphingosine bases, whereas pig and human ceramides also contain phytosphingosine

  12. Sphingolipid metabolism in organotypic mouse keratinocyte cultures

    Madison, K.C.; Swartzendruber, D.C.; Wertz, P.W.; Downing, D.T. (Univ. of Iowa College of Medicine, Iowa City (USA))


    Ceramides are the dominant component of the stratum corneum intercellular lipid lamellae, which constitute the epidermal permeability barrier. Only pig and human epidermal ceramides have been extensively characterized and the structures of the ceramides of cultured keratinocytes have not been previously investigated. In the present studies, we have characterized the ceramides synthesized by organotypic lifted mouse keratinocyte cultures for the first time and compared them to the ceramides of intact mouse epidermis. Both mouse epidermis and cultures contained five ceramides, ceramide 1 being the least polar and ceramide 5 the most polar. Ceramide 1 was a group of acylceramides, i.e., very-long-chain omega-hydroxyceramides with an ester-linked nonhydroxy fatty acid. Ceramide 2 contained medium-length saturated nonhydroxy fatty acids. (In culture, the ceramide 2 band was split into two parts with the slightly more polar ceramide 2' containing short-chain saturated nonhydroxy fatty acids.) Ceramide 5 contained short-chain alpha-hydroxy fatty acids. The structures of ceramides 1, 2, and 5 were analagous to those of pig and human epidermis. Mouse epidermal ceramide 3 was quite unusual, containing beta-hydroxy fatty acids, a structure not previously identified among mammalian ceramides. In contrast, culture ceramide 3 was composed of omega-hydroxy fatty acids with a chain-length distribution similar to that of ceramide 1. Mouse ceramide 4 was composed of fatty acids with chromatographic mobility similar to hydroxy fatty acids but with different chemical reactivity; it remains only partially characterized. Culture ceramide 4 was present in quantities too small for analysis. All ceramides in mouse epidermis and cultures contained only sphingosine bases, whereas pig and human ceramides also contain phytosphingosine.

  13. Infra Red 3D Computer Mouse

    Harbo, Anders La-Cour; Stoustrup, Jakob


    The infra red 3D mouse is a three dimensional input device to a computer. It works by determining the position of an arbitrary object (like a hand) by emitting infra red signals from a number of locations and measuring the reflected intensities. To maximize stability, robustness, and use of bandw......The infra red 3D mouse is a three dimensional input device to a computer. It works by determining the position of an arbitrary object (like a hand) by emitting infra red signals from a number of locations and measuring the reflected intensities. To maximize stability, robustness, and use...

  14. Primary monolayer culture of adult mouse hepatocytes

    Primary monolayer cultures of adult mouse hepatocytes isolated by collagenase perfusion of the liver in situ were exposed to 2 hepatotropic viruses, an avian influenza A virus adapted to grow in mouse liver in vivo and a herpes simplex type I virus. Influenza virus infection led to lysis of individual hepatocytes and total monolayer destruction within 18 to 120 hours after infection according to the virus dose used. Virus replication was evidenced by assaying hepatocyte supernates for hemagglutinin and infectivity, immunofluorescent staining and by electron microscopy. Herpes virus infection resulted in polykaryocyte formation followed by nuclear pycnosis and cell lysis. Virus replication was assayed by titration of supernate infectivity. (auth.)

  15. Pendulum Sensor using an Optical Mouse

    Peters, Randall D


    An optical mouse that is in common use with personal computers is employed to measure the motion of a pendulum. The pendulum can be monitored (i) realtime only, or (ii) also with data storage for later detailed analysis using Excel. The software developed for this purpose is a LabView executable algorithm. It allows the user to select among several modes that include filtering operations. The limiting resolution of this position sensor, which is in the neighborhood of 50 micrometers, is determined by the 'dpi' specification of the mouse.

  16. A Color Based Touchless Finger Mouse

    Kah-Meng Kwong


    Full Text Available People work with computers almost anytime, everywhere  in the current trend. However, continuously controlling a computer with mouse for a long time might cause much strains to people’s wrist. This work proposes a touchless finger mouse using webcam. A marker with different colours representing different actions is used. The webcam will capture the information on the marker and trigger the associated actions. This prototype is proven to be able to perform most of the actions a normal mouser can perform.

  17. Scimetrics开发Kaput Mouse Blocks



    Scimetrics公司开发出Kaput Mouse Blocks来杀灭麇鼠和白足鼠,这两种害鼠传播汉他病毒和lyme病,该产品的关键有效成分为杀鼠灵,对非靶标动物表现出次级毒性。Kaput Mouse Blocks是唯一获准EPA许可的用于杀灭麇鼠和白足鼠的产品。

  18. The wobbler mouse, an ALS animal model

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas


    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...... disease mechanism and testing various therapeutic approaches and discuss the relevance of these advances for human ALS. The identification of the causative mutation linking the wobbler mutation to a vesicle transport factor and the research focussed on the cellular basis and the therapeutic treatment of...

  19. Recovery Outline: New Mexico Jumping Mouse (Zapus hudsonius luteus)

    US Fish and Wildlife Service, Department of the Interior — The purpose of this recovery outline is to provide an interim strategy to guide the conservation and recovery of the New Mexico meadow jumping mouse (jumping mouse)...

  20. Recombinant mouse interferon-gamma regulation of antibody production.

    Johnson, H M; Torres, B A


    Interferon-gamma produced in monkey cells by transfection with mouse interferon-gamma cDNA suppressed the mouse in vitro antibody response in a manner similar to that of natural mouse interferon-gamma. Significant suppression was obtained with as little as 1 U of interferon. Recombinant human interferon-gamma produced by cloning in a similar fashion was not suppressive. Both the suppressive and the antiviral activities of recombinant interferon-gamma were neutralized by antibodies to mouse na...

  1. Intraspinal transplantation of mouse and human neural precursor cells

    Weinger, Jason G.; Chen, Lu; Coleman, Ronald; Leang, Ronika; Plaisted, Warren C.; Loring, Jeanne F.; Lane, Thomas E


    This unit describes the preparation and transplantation of human neural precursor cells (hNPCs) and mouse neural precursor cells (mNPCs) into the thoracic region of the mouse spinal cord. The techniques in this unit also describe how to prepare the mouse for surgery by performing a laminectomy to expose the spinal cord for transplantation. Here we show NPCs genetically labeled with eGFP transplanted into the spinal cord of a mouse following viralmediated demyelination can efficiently be detec...

  2. Sequence and chromosomal localization of the mouse brevican gene

    Rauch, U; Meyer, H; Brakebusch, C;


    Brevican is a brain-specific proteoglycan belonging to the aggrecan family. Phage clones containing the complete mouse brevican open reading frame of 2649 bp and the complete 3'-untranslated region of 341 bp were isolated from a mouse brain cDNA library, and cosmid clones containing the mouse...

  3. 9 CFR 113.33 - Mouse safety tests.


    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic...

  4. Having Fun with a Cordless Mouse

    Nunn, John


    A cordless mouse with an added reed switch is used as a wireless data logger to record every time the wheel of a trolley completes a revolution. The limitations of the system in terms of maximum clicking rate and spatial resolution are considered and data obtained from the descent of a trolley down a ramp at various different angles is analysed in…

  5. Somatic Cell Nuclear Transfer in the Mouse

    Kishigami, Satoshi; Wakayama, Teruhiko

    Somatic cell nuclear transfer (SCNT) has become a unique and powerful tool for epigenetic reprogramming research and gene manipulation in animals since “Dolly,” the first animal cloned from an adult cell was reported in 1997. Although the success rates of somatic cloning have been inefficient and the mechanism of reprogramming is still largely unknown, this technique has been proven to work in more than 10 mammalian species. Among them, the mouse provides the best model for both basic and applied research of somatic cloning because of its abounding genetic resources, rapid sexual maturity and propagation, minimal requirements for housing, etc. This chapter describes a basic protocol for mouse cloning using cumulus cells, the most popular cell type for NT, in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. In particular, we focus on a new, more efficient mouse cloning protocol using trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, which increases both in vitro and in vivo developmental rates from twofold to fivefold. This new method including TSA will be helpful to establish mouse cloning in many laboratories.

  6. Immunohistochemistry of Paraffin Sections from Mouse Ovaries.

    Akkoyunlu, Gokhan; Tepekoy, Filiz


    Immunohistochemistry (IHC) is an efficient technique to detect cellular localizations of the proteins in paraffin-embedded tissues. It allows specific proteins to be visualized by the interaction of antibodies with an enzyme-substrate-chromogen system. Here, we describe indirect immunohistochemistry method for paraffin-embedded mouse ovaries fixed with Bouin's Fixative. PMID:27557588

  7. On a new Mouse from Java

    Jentink, F.A.


    A mouse, collected by Mr. Bartels, April 1903, at an altitude of 6000 feet on the Pangerango-mountain, Java, was presented by that gentleman to our Museum. In comparing it with our Javan Mice I see that the animal differs enough to bestow it with a new specific title. Superficially it reminds my Mus

  8. MPHASYS: a mouse phenotype analysis system

    Mian I


    Full Text Available Abstract Background Systematic, high-throughput studies of mouse phenotypes have been hampered by the inability to analyze individual animal data from a multitude of sources in an integrated manner. Studies generally make comparisons at the level of genotype or treatment thereby excluding associations that may be subtle or involve compound phenotypes. Additionally, the lack of integrated, standardized ontologies and methodologies for data exchange has inhibited scientific collaboration and discovery. Results Here we introduce a Mouse Phenotype Analysis System (MPHASYS, a platform for integrating data generated by studies of mouse models of human biology and disease such as aging and cancer. This computational platform is designed to provide a standardized methodology for working with animal data; a framework for data entry, analysis and sharing; and ontologies and methodologies for ensuring accurate data capture. We describe the tools that currently comprise MPHASYS, primarily ones related to mouse pathology, and outline its use in a study of individual animal-specific patterns of multiple pathology in mice harboring a specific germline mutation in the DNA repair and transcription-specific gene Xpd. Conclusion MPHASYS is a system for analyzing multiple data types from individual animals. It provides a framework for developing data analysis applications, and tools for collecting and distributing high-quality data. The software is platform independent and freely available under an open-source license 1.

  9. An update on the mouse liver proteome

    Borlak Jürgen


    Full Text Available Abstract Background Decoding of the liver proteome is subject of intense research, but hampered by methodological constraints. We recently developed an improved protocol for studying rat liver proteins based on 2-DE-MALDI-TOF-MS peptide mass finger printing. This methodology was now applied to develop a mouse liver protein database. Results Liver proteins were extracted by two different lysis buffers in sequence followed by a liquid-phase IEF pre-fractionation and separation of proteins by 2 DE at two different pH ranges, notably 5-8 and 7-10. Based on 9600 in gel digests a total of 643 mouse liver proteins with high sequence coverage (> 20 peptides per protein could be identified by MALDI-TOF-MS peptide mass finger printing. Notably, 255 proteins are novel and have not been reported so far by conventional two-dimensional electrophoresis proteome mapping. Additionally, the results of the present findings for mouse liver were compared to published data of the rat proteome to compile as many proteins as possible in a rodent liver database. Conclusion Based on 2-DE MALDI-TOF-MS a significantly improved proteome map of mouse liver was obtained. We discuss some prominent members of newly identified proteins for a better understanding of liver biology.

  10. An elemental microanalysis of mouse ileum tissue

    A scanning proton microprobe has been used for a preliminary investigation of the cellular distribution of heavy metals and other elements in mouse ileum tissue. In order to study the cellular and elemental morphology of a villus the spatial distributions of the yields of characteristic X-rays are compared to a photomicrograph of the irradiated tissue and to a stained adjacent tissue section

  11. Hantavirus in African Wood Mouse, Guinea

    Klempa, Boris; Fichet-Calvet, Elisabeth; Lecompte, Emilie; Auste, Brita; Aniskin, Vladimir; Meisel, Helga; Denys, Christiane; Koivogui, Lamine; ter Meulen, Jan; Krüger, Detlev H.


    Hantaviruses are rodentborne, emerging viruses that cause life-threatening human diseases in Eurasia and the Americas. We detected hantavirus genome sequences in an African wood mouse (Hylomyscus simus) captured in Sangassou, Guinea. Sequence and phylogenetic analyses of the genetic material demonstrate a novel hantavirus species, which we propose to name "Sangassou virus."

  12. Dental apoptosis machinery in the mouse

    Matalová, Eva; Sharpe, P. T.; Šetková, Jana; Míšek, Ivan; Tucker, A. S.

    Cold Spring: Cold Spring Harbor Laboratory, 2006. s. 1-1. [19th annual meeting on Mouse Molecular Genetics. 30.08.2006-03.09.2006, Cold Spring Harbor Laboratory] R&D Projects: GA ČR GA304/04/0101 Institutional research plan: CEZ:AV0Z50450515 Keywords : dental apoptosis machinery Subject RIV: EA - Cell Biology

  13. Progress of gene targeting in mouse


    Gene targeting is a powerful approach of study- ing the genefunction in vivo. Specific genetic modifications, including simple gene disruption, point mutations, large chromosomal deletions and rearrangements, targeted incor- poration of foreign genes, could be introduced into the mouse genome by gene targeting. Recent studies make it possible to do the gene targeting with temporal and spatial control.

  14. Sphingolipid metabolism in organotypic mouse keratinocyte cultures.

    Madison, K C; Swartzendruber, D C; Wertz, P W; Downing, D T


    Ceramides are the dominant component of the stratum corneum intercellular lipid lamellae, which constitute the epidermal permeability barrier. Only pig and human epidermal ceramides have been extensively characterized and the structures of the ceramides of cultured keratinocytes have not been previously investigated. In the present studies, we have characterized the ceramides synthesized by organotypic lifted mouse keratinocyte cultures for the first time and compared them to the ceramides of intact mouse epidermis. Both mouse epidermis and cultures contained five ceramides, ceramide 1 being the least polar and ceramide 5 the most polar. Ceramide 1 was a group of acylceramides, i.e., very-long-chain omega-hydroxyceramides with an ester-linked nonhydroxy fatty acid. Ceramide 2 contained medium-length saturated nonhydroxy fatty acids. (In culture, the ceramide 2 band was split into two parts with the slightly more polar ceramide 2' containing short-chain saturated nonhydroxy fatty acids.) Ceramide 5 contained short-chain alpha-hydroxy fatty acids. The structures of ceramides 1, 2, and 5 were analagous to those of pig and human epidermis. Mouse epidermal ceramide 3 was quite unusual, containing beta-hydroxy fatty acids, a structure not previously identified among mammalian ceramides. In contrast, culture ceramide 3 was composed of omega-hydroxy fatty acids with a chain-length distribution similar to that of ceramide 1. Mouse ceramide 4 was composed of fatty acids with chromatographic mobility similar to hydroxy fatty acids but with different chemical reactivity; it remains only partially characterized. Culture ceramide 4 was present in quantities too small for analysis. All ceramides in mouse epidermis and cultures contained only sphingosine bases, whereas pig and human ceramides also contain phytosphingosine. These results indicate that considerable diversity of ceramide structures occurs among mammalian species and that cultured keratinocytes may only partially

  15. Stimulation of mouse DNA primase-catalyzed oligoribonucleotide synthesis by mouse DNA helicase B.

    Saitoh, A; S. Tada; Katada, T; Enomoto, T.


    Many prokaryotic and viral DNA helicases involved in DNA replication stimulate their cognate DNA primase activity. To assess the stimulation of DNA primase activity by mammalian DNA helicases, we analyzed the synthesis of oligoribonucleotides by mouse DNA polymerase alpha-primase complex on single-stranded circular M13 DNA in the presence of mouse DNA helicase B. DNA helicase B was purified by sequential chromatography through eight columns. When the purified DNA helicase B was applied to a M...

  16. MouseMine: a new data warehouse for MGI.

    Motenko, H; Neuhauser, S B; O'Keefe, M; Richardson, J E


    MouseMine ( is a new data warehouse for accessing mouse data from Mouse Genome Informatics (MGI). Based on the InterMine software framework, MouseMine supports powerful query, reporting, and analysis capabilities, the ability to save and combine results from different queries, easy integration into larger workflows, and a comprehensive Web Services layer. Through MouseMine, users can access a significant portion of MGI data in new and useful ways. Importantly, MouseMine is also a member of a growing community of online data resources based on InterMine, including those established by other model organism databases. Adopting common interfaces and collaborating on data representation standards are critical to fostering cross-species data analysis. This paper presents a general introduction to MouseMine, presents examples of its use, and discusses the potential for further integration into the MGI interface. PMID:26092688

  17. Having fun with a cordless mouse

    Nunn, John


    A cordless mouse with an added reed switch is used as a wireless data logger to record every time the wheel of a trolley completes a revolution. The limitations of the system in terms of maximum clicking rate and spatial resolution are considered and data obtained from the descent of a trolley down a ramp at various different angles is analysed in different ways. The data is analysed to obtain initial accelerations (down the ramp) and subsequent decelerations (on the flat), as well as maximum velocities, and these results are used to compare the actual performance of the trolley (with friction) with the theoretical expectation. An agreement of better than 2% on the value of gravity is obtained. Encouraging agreement on frictional forces (and accelerations) is also obtained by considering the maximum kinetic energies reached at the bottom of the ramp. This paper includes the free provision of custom software to record the time history of the clicking of a mouse.

  18. Histomorphological Phenotyping of the Adult Mouse Brain.

    Mikhaleva, Anna; Kannan, Meghna; Wagner, Christel; Yalcin, Binnaz


    This article describes a series of standard operating procedures for morphological phenotyping of the mouse brain using basic histology. Many histological studies of the mouse brain use qualitative approaches based on what the human eye can detect. Consequently, some phenotypic information may be missed. Here we describe a quantitative approach for the assessment of brain morphology that is simple and robust. A total of 78 measurements are made throughout the brain at specific and well-defined regions, including the cortex, the hippocampus, and the cerebellum. Experimental design and timeline considerations, including strain background effects, the importance of sectioning quality, measurement variability, and efforts to correct human errors are discussed. © 2016 by John Wiley & Sons, Inc. PMID:27584555

  19. Mouse cell culture - Methods and protocols

    CarloAlberto Redi


    Full Text Available The mouse is, out of any doubt, the experimental animal par excellence for many many colleagues within the scientific community, notably for those working in mammalian biology (in a broad sense, from basic genetic to modeling human diseases, starting at least from 1664 Robert Hooke experiments on air’s propertyn. Not surprising then that mouse cell cultures is a well established field of research itself and that there are several handbooks devoted to this discipline. Here, Andrew Ward and David Tosh provide a necessary update of the protocols currently needed. In fact, nearly half of the book is devoted to stem cells culture protocols, mainly embryonic, from a list of several organs (kidney, lung, oesophagus and intestine, pancreas and liver to mention some........

  20. Radiation response of the mouse tongue epithelium

    Mouse tongue mucosa has been used as a model to study dose responses to local irradiation. Although the irradiation procedures is less feasible and more time-consuming than e.g. snout irradiation, the tongue is the only location where a reasonable area of intraoral, multilayered epithelium in the mouse can be locally treated and scored, and a relatively small burden is imposed on the animal. In pilot experiments with external 300 kV x-irradiation just tolerated by the lip, the authors did not see critical damage to the tongue. In the present model, the onset of denudation was not correctly predicted by the normal turnover time of the tissue. (UK)


    Šimeček, Petr; Dzúr-Gejdošová, Mária; Chvátalová, I.; Forejt, Jiří

    SETUBAL, PORTUGAL: SCITEPRESS, AV D MANUELL, 27A 2 ESQ, SETUBAL, 2910-595, PORTUGAL, 2011, s. 238-243. ISBN 978-989-8425-36-2. [BIOINFORMATICS 2011, Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms. Setubal (PT), 26.01.2011-29.01.2011] Institutional support: RVO:68378050 Keywords : Litter effect * Mixed-effect models * Phenome databases * Mouse genetics Subject RIV: EB - Genetics ; Molecular Biology

  2. Mouse Genetic Models of Human Brain Disorders

    Celeste eLeung; Zhengping eJia


    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectua...

  3. An update on the mouse liver proteome

    Borlak Jürgen; Gazzana Giuseppe


    Abstract Background Decoding of the liver proteome is subject of intense research, but hampered by methodological constraints. We recently developed an improved protocol for studying rat liver proteins based on 2-DE-MALDI-TOF-MS peptide mass finger printing. This methodology was now applied to develop a mouse liver protein database. Results Liver proteins were extracted by two different lysis buffers in sequence followed by a liquid-phase IEF pre-fractionation and separation of proteins by 2 ...

  4. Making the blastocyst: lessons from the mouse

    Cockburn, Katie; Rossant, Janet


    Mammalian preimplantation development, which is the period extending from fertilization to implantation, results in the formation of a blastocyst with three distinct cell lineages. Only one of these lineages, the epiblast, contributes to the embryo itself, while the other two lineages, the trophectoderm and the primitive endoderm, become extra-embryonic tissues. Significant gains have been made in our understanding of the major events of mouse preimplantation development, and recent discoveri...

  5. Exploring Images: A Haptic Mouse Approach

    James Wolfer


    Full Text Available Exposing students to touch-enabled computing typically requires the use of expensive Haptic robots. This exhibit demonstrates the adaptation of a commercial, haptically-enabled mouse. Using a customized Linux device driver and a Python imaging script, we allow users to “virtually touch” images. Specific examples include exploring the Mona Lisa, digital mammograms, and ”touch-traversal” of a maze.

  6. Communication compartments in the gastrulating mouse embryo


    We characterized the pattern of gap junctional communication in the 7.5- d mouse embryo (at the primitive streak or gastrulation stage). First we examined the pattern of dye coupling by injecting the fluorescent tracers, Lucifer Yellow or carboxyfluorescein, and monitoring the extent of dye spread. These studies revealed that cells within all three germ layers are well coupled, as the injected dye usually spread rapidly from the site of impalement into the neighboring cells. The dye spread, h...

  7. Characterization of Mouse IFT Complex B

    Follit, John A.; Xu, Fenghui; Keady, Brian; Pazour, Gregory J.


    The primary cilium plays a key role in the development of mammals and in the maintenance of health. Primary cilia are assembled and maintained by the process of intraflagellar transport (IFT). In this work, we characterize mouse IFT complex B by identifying all of the mammalian orthologues of complex B and B-associated proteins previously identified in Chlamydomonas and Caenorhabditis and also identify a new component (IFT25/Hspb11) of complex B by database analysis. We tagged each of these p...

  8. Cranial bone morphometric study among mouse strains

    Yamamura Ken-ichi; Kawakami Minoru


    Abstract Background Little is known about the molecular mechanism which regulates how the whole cranium is shaped. Mouse models currently available for genetic research include several hundreds of unique inbred strains and genetically engineered mutants. By cross comparing their genomic structures, we can elucidate the cause of any differences in the phenotype between two strains. The craniometry of subspecies, or closely related species, of mice provide a good systemic model to study the rel...

  9. Genetically engineered mouse models of pituitary tumors

    DavidACano; AlfonsoSoto-Moreno


    Animal models constitute valuable tools for investigating the pathogenesis of cancer as well as for preclinical testing of novel therapeutics approaches. However, the pathogenic mechanisms of pituitary tumor formation remain poorly understood, particularly in sporadic adenomas, thus making it a challenge to model pituitary tumors in mice. Nevertheless, genetically engineered mouse models (GEMMs) of pituitary tumors have provided important insight into pituitary tumor biology. In this paper, w...

  10. DNA damage response during mouse oocyte maturation

    Mayer, Alexandra; Baran, Vladimír; Sakakibara, Y.; Brzáková, Adéla; Ferencová, Ivana; Motlík, Jan; Kitajima, T.; Schultz, R. M.; Šolc, Petr


    Roč. 15, č. 4 (2016), s. 546-558. ISSN 1538-4101 R&D Projects: GA MŠk LH12057; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : double strand DNA breaks * DNA damage * MRE11 * meiotic maturation * mouse oocytes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.565, year: 2014

  11. Digenic Inheritance in Cystinuria Mouse Model.

    Meritxell Espino

    Full Text Available Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5-months and late stage (8-months of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/- present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/- and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients.

  12. Biological characteristics of mouse skin melanocytes.

    Shi, Zhanquan; Ji, Kaiyuan; Yang, Shanshan; Zhang, Junzhen; Yao, Jianbo; Dong, Changsheng; Fan, Ruiwen


    The objective of this research was to evaluate the optimal passage number according to the biological characteristics of mouse skin melanocytes from different passages. Skin punch biopsies harvested from the dorsal region of 2-day old mice were used to establish melanocyte cultures. The cells from passage 4, 7, 10 and 13 were collected and evaluated for their melanogenic activity. Histochemical staining for tyrosinase (TYR) activity and immunostaining for the melanocyte specific markers including S-100 antigen, TYR, tyrosinase related protein 1 (TYRP1), tyrosinase related protein 2 (TYRP2) and micropthalmia associated transcription factor (MITF) confirmed purity and melanogenic capacity of melanocytes from different passages, with better melanogenic activity of passage 10 and 13 cells being observed. Treatment of passage 13 melanocytes with α-melanocyte stimulating hormone (α-MSH) showed increased expression of MITF, TYR and TYRP2 mRNA. However, considering the TYR mRNA dramatically high expression which is the characteristics of melanoma cells, melanocytes from passage 10 was the optimal passage number for the further research. Our results demonstrate culture of pure populations of mouse melanocytes to at least 10 passages and illustrate the potential utility of passage 10 cells for studies of intrinsic and extrinsic regulation of genes controlling pigmentation and coat color in mouse. PMID:26905193

  13. The Mouse Clock Locus: Sequence and Comparative Analysis of 204 Kb from Mouse Chromosome 5

    Wilsbacher, Lisa D.; Sangoram, Ashvin M.; Antoch, Marina P.; Takahashi, Joseph S.


    The Clock gene encodes a basic helix-loop-helix (bHLH)–PAS transcription factor that regulates circadian rhythms in mice. We previously cloned Clock in mouse and human using a battery of behavioral and molecular techniques, including shotgun sequencing of two bacterial artificial chromosome (BAC) clones. Here we report the finished sequence of a 204-kb region from mouse chromosome 5. This region contains the complete loci for the Clock and Tpardl (pFT27) genes, as well as the 3′ partial locus...

  14. Laminar circuit organization and response modulation in mouse visual cortex

    Victor Quintanar-Zilinskas; Xiangmin Xu


    The mouse has become an increasingly important animal model for visual system studies, but few studies have investigated local functional circuit organization of mouse visual cortex. Here we used our newly developed mapping technique combining laser scanning photostimulation (LSPS) with fast voltage-sensitive dye (VSD) imaging to examine the spatial organization and temporal dynamics of laminar circuit responses in living slice preparations of mouse primary visual cortex (V1). During experi...

  15. A Chemical Mutagenesis Screen Identifies Mouse Models with ERG Defects.

    Charette, Jeremy R; Samuels, Ivy S; Yu, Minzhong; Stone, Lisa; Hicks, Wanda; Shi, Lan Ying; Krebs, Mark P; Naggert, Jürgen K; Nishina, Patsy M; Peachey, Neal S


    Mouse models provide important resources for many areas of vision research, pertaining to retinal development, retinal function and retinal disease. The Translational Vision Research Models (TVRM) program uses chemical mutagenesis to generate new mouse models for vision research. In this chapter, we report the identification of mouse models for Grm1, Grk1 and Lrit3. Each of these is characterized by a primary defect in the electroretinogram. All are available without restriction to the research community. PMID:26427409

  16. Criteria for Validating Mouse Models of Psychiatric Diseases

    Chadman, Kathryn K.; Yang, Mu; Crawley, Jacqueline N.


    Animal models of human diseases are in widespread use for biomedical research. Mouse models with a mutation in a single gene or multiple genes are excellent research tools for understanding the role of a specific gene in the etiology of a human genetic disease. Ideally, the mouse phenotypes will recapitulate the human phenotypes exactly. However, exact matches are rare, particularly in mouse models of neuropsychiatric disorders. This article summarizes the current strategies for optimizing th...

  17. Patterning by heritage in mouse molar row development

    Prochazka, Jan; Pantalacci, Sophie; Churava, Svatava; Rothova, Michaela; Lambert, Anne; Lesot, Hervé; Klein, Ophir; Peterka, Miroslav; Laudet, Vincent; Peterkova, Renata


    It is known from paleontology studies that two premolars have been lost during mouse evolution. During mouse mandible development, two bud-like structures transiently form that may represent rudimentary precursors of the lost premolars. However, the interpretation of these structures and their significance for mouse molar development are highly controversial because of a lack of molecular data. Here, we searched for typical tooth signaling centers in these two bud-like structures, and followe...

  18. The treatment of a severe ataxic dysarthria, using electropalatography. Single case study

    Main, Alison; Kelly, Stephen W.; Manley, Graham


    Electropalatography has been used successfully with several client groups (Hardcastle et al 1991). Intelligibility has been improved in children with articulation difficulties as a result of cleft palate, or with dyspraxia, or long standing phonological difficulties. There has been less work with adults and a very limited amount with acquired dysarthrics (Gibbon 1997). In the majority of cases reported, there has been a degree of improvement in intelligibility (eg Goldstein et al 1994). This ...

  19. Mouse Model of Coxiella burnetii Aerosolization.

    Melenotte, Cléa; Lepidi, Hubert; Nappez, Claude; Bechah, Yassina; Audoly, Gilles; Terras, Jérôme; Raoult, Didier; Brégeon, Fabienne


    Coxiella burnetii is mainly transmitted by aerosols and is responsible for multiple-organ lesions. Animal models have shown C. burnetii pathogenicity, but long-term outcomes still need to be clarified. We used a whole-body aerosol inhalation exposure system to mimic the natural route of infection in immunocompetent (BALB/c) and severe combined immunodeficient (SCID) mice. After an initial lung inoculum of 10(4) C. burnetii cells/lung, the outcome, serological response, hematological disorders, and deep organ lesions were described up to 3 months postinfection. C. burnetii-specific PCR, anti-C. burnetii immunohistochemistry, and fluorescent in situ hybridization (FISH) targeting C. burnetii-specific 16S rRNA completed the detection of the bacterium in the tissues. In BALB/c mice, a thrombocytopenia and lymphopenia were first observed, prior to evidence of C. burnetii replication. In all SCID mouse organs, DNA copies increased to higher levels over time than in BALB/c ones. Clinical signs of discomfort appeared in SCID mice, so follow-up had to be shortened to 2 months in this group. At this stage, all animals presented bone, cervical, and heart lesions. The presence of C. burnetii could be attested in situ for all organs sampled using immunohistochemistry and FISH. This mouse model described C. burnetii Nine Mile strain spread using aerosolization in a way that corroborates the pathogenicity of Q fever described in humans and completes previously published data in mouse models. C. burnetii infection occurring after aerosolization in mice thus seems to be a useful tool to compare the pathogenicity of different strains of C. burnetii. PMID:27160294

  20. A humanized mouse model of tuberculosis.

    Veronica E Calderon

    Full Text Available Mycobacterium tuberculosis (M.tb is the second leading infectious cause of death worldwide and the primary cause of death in people living with HIV/AIDS. There are several excellent animal models employed to study tuberculosis (TB, but many have limitations for reproducing human pathology and none are amenable to the direct study of HIV/M.tb co-infection. The humanized mouse has been increasingly employed to explore HIV infection and other pathogens where animal models are limiting. Our goal was to develop a small animal model of M.tb infection using the bone marrow, liver, thymus (BLT humanized mouse. NOD-SCID/γc(null mice were engrafted with human fetal liver and thymus tissue, and supplemented with CD34(+ fetal liver cells. Excellent reconstitution, as measured by expression of the human CD45 pan leukocyte marker by peripheral blood populations, was observed at 12 weeks after engraftment. Human T cells (CD3, CD4, CD8, as well as natural killer cells and monocyte/macrophages were all observed within the human leukocyte (CD45(+ population. Importantly, human T cells were functionally competent as determined by proliferative capacity and effector molecule (e.g. IFN-γ, granulysin, perforin expression in response to positive stimuli. Animals infected intranasally with M.tb had progressive bacterial infection in the lung and dissemination to spleen and liver from 2-8 weeks post infection. Sites of infection in the lung were characterized by the formation of organized granulomatous lesions, caseous necrosis, bronchial obstruction, and crystallization of cholesterol deposits. Human T cells were distributed throughout the lung, liver, and spleen at sites of inflammation and bacterial growth and were organized to the periphery of granulomas. These preliminary results demonstrate the potential to use the humanized mouse as a model of experimental TB.

  1. Mouse allergen-specific immunoglobulin G4 and risk of mouse skin test sensitivity

    E.C. Matsui; G.B. Diette; E.J.M. Krop; R.C. Aalberse; A.L. Smith; P.A. Eggleston


    Background High serum levels of cat-specific IgG and IgG4 are associated with protection against allergic sensitization to cat, but whether this association applies to other animal allergens remains unclear. Objective To determine if high levels of mouse-specific IgG and IgG4 are associated with a d

  2. Genetically engineered mouse models of pituitary tumors



    Full Text Available Animal models constitute valuable tools for investigating the pathogenesis of cancer as well as for preclinical testing of novel therapeutics approaches. However, the pathogenic mechanisms of pituitary tumor formation remain poorly understood, particularly in sporadic adenomas, thus making it a challenge to model pituitary tumors in mice. Nevertheless, genetically engineered mouse models (GEMMs of pituitary tumors have provided important insight into pituitary tumor biology. In this paper, we review various GEMMs of pituitary tumors, highlighting their contributions and limitations, and discuss opportunities for research in the field.

  3. A Mouse Model for Human Anal Cancer

    Stelzer, Marie K.; Pitot, Henry C.; Liem, Amy; Schweizer, Johannes; Mahoney, Charles; Lambert, Paul F.


    Human anal cancers are associated with high-risk human papillomaviruses (HPVs) that cause other anogenital cancers and head and neck cancers. As with other cancers, HPV16 is the most common high-risk HPV in anal cancers. We describe the generation and characterization of a mouse model for human anal cancer. This model makes use of K14E6 and K14E7 transgenic mice in which the HPV16 E6 and E7 genes are directed in their expression to stratified squamous epithelia. HPV16 E6 and E7 possess oncoge...

  4. A mouse model of in utero transplantation.

    Nijagal, Amar; Le, Tom; Wegorzewska, Marta; Mackenzie, Tippi C


    The transplantation of stem cells and viruses in utero has tremendous potential for treating congenital disorders in the human fetus. For example, in utero transplantation (IUT) of hematopoietic stem cells has been used to successfully treat patients with severe combined immunodeficiency. In several other conditions, however, IUT has been attempted without success. Given these mixed results, the availability of an efficient non-human model to study the biological sequelae of stem cell transplantation and gene therapy is critical to advance this field. We and others have used the mouse model of IUT to study factors affecting successful engraftment of in utero transplanted hematopoietic stem cells in both wild-type mice and those with genetic diseases. The fetal environment also offers considerable advantages for the success of in utero gene therapy. For example, the delivery of adenoviral, adeno-associated viral, retroviral, and lentiviral vectors into the fetus has resulted in the transduction of multiple organs distant from the site of injection with long-term gene expression. in utero gene therapy may therefore be considered as a possible treatment strategy for single gene disorders such as muscular dystrophy or cystic fibrosis. Another potential advantage of IUT is the ability to induce immune tolerance to a specific antigen. As seen in mice with hemophilia, the introduction of Factor IX early in development results in tolerance to this protein. In addition to its use in investigating potential human therapies, the mouse model of IUT can be a powerful tool to study basic questions in developmental and stem cell biology. For example, one can deliver various small molecules to induce or inhibit specific gene expression at defined gestational stages and manipulate developmental pathways. The impact of these alterations can be assessed at various timepoints after the initial transplantation. Furthermore, one can transplant pluripotent or lineage specific progenitor

  5. Mouse models for understanding human developmental anomalies

    The mouse experimental system presents an opportunity for studying the nature of the underlying mutagenic damage and the molecular pathogenesis of this class of anomalies by virtue of the accessibility of the zygote and its descendant blastomeres. Such studies could contribute to the understanding of the etiology of certain sporadic but common human malformations. The vulnerability of the zygotes to mutagens as demonstrated in the studies described in this report should be a major consideration in chemical safety evaluation. It raises questions regarding the danger to human zygotes when the mother is exposed to drugs and environmental chemicals

  6. Taxonomy Icon Data: house mouse [Taxonomy Icon

    Full Text Available house mouse Mus musculus Chordata/Vertebrata/Mammalia/Theria/Eutheria/etc. Mus_musculus_L.png Mus_musculus..._NL.png Mus_musculus_S.png Mus_musculus_NS.png ...

  7. Optogenetic Control of Mouse Outer Hair Cells.

    Wu, Tao; Ramamoorthy, Sripriya; Wilson, Teresa; Chen, Fangyi; Porsov, Edward; Subhash, Hrebesh; Foster, Sarah; Zhang, Yuan; Omelchenko, Irina; Bateschell, Michael; Wang, Lingyan; Brigande, John V; Jiang, Zhi-Gen; Mao, Tianyi; Nuttall, Alfred L


    Normal hearing in mammals depends on sound amplification by outer hair cells (OHCs) presumably by their somatic motility and force production. However, the role of OHC force production in cochlear amplification and frequency tuning are not yet fully understood. Currently, available OHC manipulation techniques for physiological or clinical studies are limited by their invasive nature, lack of precision, and poor temporal-spatial resolution. To overcome these limitations, we explored an optogenetic approach based on channelrhodopsin 2 (ChR-2), a direct light-activated nonselective cation channel originally discovered in Chlamydomonas reinhardtii. Three approaches were compared: 1) adeno-associated virus-mediated in utero transfer of the ChR-2 gene into the developing murine otocyst, 2) expression of ChR-2(H134R) in an auditory cell line (HEI-OC1), and 3) expression of ChR-2 in the OHCs of a mouse line carrying a ChR-2 conditional allele. Whole cell recording showed that blue light (470 nm) elicited the typical nonselective cation current of ChR-2 with reversal potential around zero in both mouse OHCs and HEI-OC1 cells and generated depolarization in both cell types. In addition, pulsed light stimulation (10 Hz) elicited a 1:1 repetitive depolarization and ChR-2 currents in mouse OHCs and HEI-OC1 cells, respectively. The time constant of depolarization in OHCs, 1.45 ms, is 10 times faster than HEI-OC1 cells, which allowed light stimulation up to rates of 10/s to elicit corresponding membrane potential changes. Our study demonstrates that ChR-2 can successfully be expressed in mouse OHCs and HEI-OC1 cells and that these present a typical light-sensitive current and depolarization. However, the amount of ChR-2 current induced in our in vivo experiments was insufficient to result in measurable cochlear effects. PMID:26789771

  8. Quantitative biometric phenotype analysis in mouse lenses

    Reilly, Matthew A.; Andley, Usha P.


    The disrupted morphology of lenses in mouse models for cataracts precludes accurate in vitro assessment of lens growth by weight. To overcome this limitation, we developed morphometric methods to assess defects in eye lens growth and shape in mice expressing the αA-crystallin R49C (αA-R49C) mutation. Our morphometric methods determine quantitative shape and dry weight of the whole lens from histological sections of the lens. This method was then used to quantitatively compare the biometric gr...

  9. Dcp1-Bodies in Mouse Oocytes

    Swetloff, Adam; Conne, Beatrice; Huarte, Joachim; Pitetti, Jean-Luc; Nef, Serge; Vassalli, Jean-Dominique


    Processing bodies (P-bodies) are cytoplasmic granules involved in the storage and degradation of mRNAs. In somatic cells, their formation involves miRNA-mediated mRNA silencing. Many P-body protein components are also found in germ cell granules, such as in mammalian spermatocytes. In fully grown mammalian oocytes, where changes in gene expression depend entirely on translational control, RNA granules have not as yet been characterized. Here we show the presence of P-body-like foci in mouse o...

  10. Involvement of mouse and porcine PLCζ-induced calcium oscillations in preimplantation development of mouse embryos

    Yoneda, Akihiro, E-mail: [Laboratory of Animal Breeding and Reproduction, Graduate School of Agriculture, Hokkaido University (Japan); Division of Molecular Therapeutics, Center for Food & Medical Innovation, Hokkaido University (Japan); Watanabe, Tomomasa [Laboratory of Animal Breeding and Reproduction, Graduate School of Agriculture, Hokkaido University (Japan)


    In mammals, phospholipase Cζ (PLCζ) has the ability to trigger calcium (Ca{sup 2+}) oscillations in oocytes, leading to oocyte activation. Although there is a species-specific difference in the PLCζ-induced Ca{sup 2+} oscillatory pattern, whether PLCζ-induced Ca{sup 2+} oscillations affect preimplantation embryonic development remains unclear. Here, we show that Ca{sup 2+} oscillations in mouse PLCζ cRNA-injected oocytes stopped just before pronuclear formation, while that in porcine PLCζ cRNA-injected oocytes continued for several hours after pronuclei had been formed. This difference of Ca{sup 2+} oscillations in oocytes after pronuclear formation was dependent on the difference in the nuclear localization signal (NLS) sequence of PLCζ between the mouse and pig. However, mouse and porcine PLCζ cRNA-injected oocytes parthenogenetically developed to blastocysts regardless of the absence or presence of Ca{sup 2+} oscillations after pronuclear formation. Furthermore, the developmental rate of mouse or porcine PLCζ-activated oocytes injected with round spermatids to the blastocyst stage was not significantly different from that of strontium-activated oocytes injected with round spermatids. These results suggest that the PLCζ-induced Ca{sup 2+} oscillatory pattern in mouse oocytes is dependent on the NLS sequence of PLCζ and injection of PLCζ may be a useful method for activation of round spermatid-injected and somatic nuclear transferred oocytes. - Highlights: • Porcine PLCζ-induced Ca{sup 2+} oscillations continued after pronuclear formation. • The Ca{sup 2+} oscillatory pattern was dependent on the difference in the NLS sequence of PLCζ. • PLCζ-activated oocytes parthenogenetically developed to blastocysts. • PLCζ-activated oocytes injected with round spermatids developed to blastocysts.

  11. Involvement of mouse and porcine PLCζ-induced calcium oscillations in preimplantation development of mouse embryos

    In mammals, phospholipase Cζ (PLCζ) has the ability to trigger calcium (Ca2+) oscillations in oocytes, leading to oocyte activation. Although there is a species-specific difference in the PLCζ-induced Ca2+ oscillatory pattern, whether PLCζ-induced Ca2+ oscillations affect preimplantation embryonic development remains unclear. Here, we show that Ca2+ oscillations in mouse PLCζ cRNA-injected oocytes stopped just before pronuclear formation, while that in porcine PLCζ cRNA-injected oocytes continued for several hours after pronuclei had been formed. This difference of Ca2+ oscillations in oocytes after pronuclear formation was dependent on the difference in the nuclear localization signal (NLS) sequence of PLCζ between the mouse and pig. However, mouse and porcine PLCζ cRNA-injected oocytes parthenogenetically developed to blastocysts regardless of the absence or presence of Ca2+ oscillations after pronuclear formation. Furthermore, the developmental rate of mouse or porcine PLCζ-activated oocytes injected with round spermatids to the blastocyst stage was not significantly different from that of strontium-activated oocytes injected with round spermatids. These results suggest that the PLCζ-induced Ca2+ oscillatory pattern in mouse oocytes is dependent on the NLS sequence of PLCζ and injection of PLCζ may be a useful method for activation of round spermatid-injected and somatic nuclear transferred oocytes. - Highlights: • Porcine PLCζ-induced Ca2+ oscillations continued after pronuclear formation. • The Ca2+ oscillatory pattern was dependent on the difference in the NLS sequence of PLCζ. • PLCζ-activated oocytes parthenogenetically developed to blastocysts. • PLCζ-activated oocytes injected with round spermatids developed to blastocysts

  12. Mouse models of anemia of cancer.

    Airie Kim

    Full Text Available Anemia of cancer (AC may contribute to cancer-related fatigue and impair quality of life. Improved understanding of the pathogenesis of AC could facilitate better treatment, but animal models to study AC are lacking. We characterized four syngeneic C57BL/6 mouse cancers that cause AC. Mice with two different rapidly-growing metastatic lung cancers developed the characteristic findings of anemia of inflammation (AI, with dramatically different degrees of anemia. Mice with rapidly-growing metastatic melanoma also developed a severe anemia by 14 days, with hematologic and inflammatory parameters similar to AI. Mice with a slow-growing peritoneal ovarian cancer developed an iron-deficiency anemia, likely secondary to chronically impaired nutrition and bleeding into the peritoneal cavity. Of the four models, hepcidin mRNA levels were increased only in the milder lung cancer model. Unlike in our model of systemic inflammation induced by heat-killed Brucella abortus, ablation of hepcidin in the ovarian cancer and the milder lung cancer mouse models did not affect the severity of anemia. Hepcidin-independent mechanisms play an important role in these murine models of AC.

  13. Germ cell transplantation in infertility mouse


    This work investigated the spermatogenesis in an infertility BALB/c-nu mouse model by reinfusing germline stem cells into seminiferous tubules.Donor germ cells were isolated from male FVB/NJ-GFP transgenic mice.Seminiferous tubule microiniection was applied to achieve intratubular germ cell transfer.The germ cells were injected into exposed testes of the infertility mice.We used green fluorescence and DNA analysis of donor cells from GFP transgenic mice as genetic marker.The natural mating and Southern blot methods were applied to analyze the effect of sperm cell transplantation and the sperm function after seminiferous tubule microinjecUon.The spermatogenesis was morphologically observed from the seminiferous tubules in 41/60(68.33%)of the injected recipient mice using allogeneic donor cells.In the colonized testes,matured spermatozoa were seen in the lumen of the seminiferous tubules.In this research,BALB/c-nu infertility mouse model,the recipient animal,was used to avoid immunological rejection of donor cells,and germ cell transplantation was applied to overcome infertility caused by busulfan treatment.These results demonstrate that this technique of germ cell transplantation is of great use.Germ cell transplantation could be potentially valuable to oncological patients.

  14. IL-6 and mouse oocyte spindle.

    Jashoman Banerjee

    Full Text Available Interleukin 6 (IL-6 is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001 as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.

  15. In vivo photoacoustic imaging of mouse embryos

    Laufer, Jan; Norris, Francesca; Cleary, Jon; Zhang, Edward; Treeby, Bradley; Cox, Ben; Johnson, Peter; Scambler, Pete; Lythgoe, Mark; Beard, Paul


    The ability to noninvasively image embryonic vascular anatomy in mouse models is an important requirement for characterizing the development of the normal cardiovascular system and malformations in the heart and vascular supply. Photoacoustic imaging, which can provide high resolution non invasive images of the vasculature based upon optical absorption by endogenous hemoglobin, is well suited to this application. In this study, photoacoustic images of mouse embryos were obtained ex vivo and in vivo. The images show intricate details of the embryonic vascular system to depths of up to 10 mm, which allowed whole embryos to be imaged in situ. To achieve this, an all-optical photoacoustic scanner and a novel time reversal image reconstruction algorithm, which provide deep tissue imaging capability while maintaining high spatial resolution and contrast were employed. This technology may find application as an imaging tool for preclinical embryo studies in developmental biology as well as more generally in preclinical and clinical medicine for studying pathologies characterized by changes in the vasculature.

  16. Characterization of mouse IFT complex B.

    Follit, John A; Xu, Fenghui; Keady, Brian T; Pazour, Gregory J


    The primary cilium plays a key role in the development of mammals and in the maintenance of health. Primary cilia are assembled and maintained by the process of intraflagellar transport (IFT). In this work, we characterize mouse IFT complex B by identifying all of the mammalian orthologues of complex B and B-associated proteins previously identified in Chlamydomonas and Caenorhabditis and also identify a new component (IFT25/Hspb11) of complex B by database analysis. We tagged each of these proteins with the FLAG epitope and show that all except IFT172 and IFT20 localize to cilia and the peri-basal body or centrosomal region at the base of cilia. All of the proteins except IFT172 immunoprecipitate IFT88 indicating that they are co-assembled into a complex. IFT20 is the only complex B protein that localizes to the Golgi apparatus. However, overexpression of IFT54/Traf3ip1, the mouse orthologue of Dyf-11/Elipsa, displaces IFT20 from the Golgi apparatus. IFT54 does not localize to the Golgi complex nor does it interact with GMAP210, which is the protein that anchors IFT20 to the Golgi apparatus. This suggests that IFT54s effect on IFT20 is a dominant negative phenotype caused by its overexpression. Cell Motil. Cytoskeleton 2009. (c) 2009 Wiley-Liss, Inc. PMID:19253336

  17. The Mouse Genome Database (MGD): premier model organism resource for mammalian genomics and genetics

    Blake, J. A.; Bult, C. J.; J.A. Kadin; J.E. Richardson; Eppig, J T


    The Mouse Genome Database (MGD) is the community model organism database for the laboratory mouse and the authoritative source for phenotype and functional annotations of mouse genes. MGD includes a complete catalog of mouse genes and genome features with integrated access to genetic, genomic and phenotypic information, all serving to further the use of the mouse as a model system for studying human biology and disease. MGD is a major component of the Mouse Genome Informatics (MGI, http://www...

  18. Endothelial and lipoprotein lipases in human and mouse placenta

    Lindegaard, Marie L S; Olivecrona, Gunilla; Christoffersen, Christina;


    protein associated with both cell types. In mouse placentas, lack of LPL expression resulted in increased EL mRNA expression. These results suggest that the cellular expression of EL and LPL in human placenta is different. Nevertheless, the two lipases might have overlapping functions in the mouse...

  19. Recognizing Student Emotions Using Brainwaves and Mouse Behavior Data

    Azcarraga, Judith; Suarez, Merlin Teodosia


    Brainwaves (EEG signals) and mouse behavior information are shown to be useful in predicting academic emotions, such as confidence, excitement, frustration and interest. Twenty five college students were asked to use the Aplusix math learning software while their brainwaves signals and mouse behavior (number of clicks, duration of each click,…

  20. Mouse Vocal Communication System: Are Ultrasounds Learned or Innate?

    Arriaga, Gustavo; Jarvis, Erich D.


    Mouse ultrasonic vocalizations (USVs) are often used as behavioral readouts of internal states, to measure effects of social and pharmacological manipulations, and for behavioral phenotyping of mouse models for neuropsychiatric and neurodegenerative disorders. However, little is known about the neurobiological mechanisms of rodent USV production.…

  1. The mammalian gene function resource: The International Knockout Mouse Consortium

    A. Bradley (Allan); K. Anastassiadis (Konstantinos); A. Ayadi (Abdelkader); J.F. Battey (James); C. Bell (Cindy); M.-C. Birling (Marie-Christine); J. Bottomley (Joanna); S.D.M. Brown (Steve); F. Bürger (Friederike); C.J. Bult (Carol); W. Bushell (Wendy); F.S. Collins (Francis); C. Desaintes (Christian); B. Doe (Brendan); E. Aris (Economides); J.T. Eppig (Janan); R.H. Finnell (Richard); C. Fletcher (Colin); M. Fray (Martin); D. Frendewey (David); R.H. Friedel (Roland); F.G. Grosveld (Frank); J. Hansen; Y. Hérault (Yann); G. Hicks (Geoffrey); A. Hörlein (Andreas); C. Houghton (Catherine); M. Hrabé De Angelis (Martin); D. Huylebroeck (Danny); V. Iyer (Vivek); P.J. de Jong (Pieter); J.A. Kadin (James); C. Kaloff (Cornelia); K. Kennedy (Karen); M. Koutsourakis (Manousos); K.C. Kent Lloyd (K.); S. Marschall (Susan); J. Mason (Jeremy); C. McKerlie (Colin); M.P. McLeod (Michael); H. von Melchner (Harald); M. Moore (Matt); A.O. Mujica (Alejandro); A. Nagy (Andras); M. Nefedov (Mikhail); L.M. Nutter (Lauryl); G. Pavlovic (Guillaume); J.L. Peterson (Jane); I. Pollock; R. Ramirez-Solis (Ramiro); D.E. Rancourt (Derrick); M. Raspa (Marcello); J.E. Remacle (Jacques); M. Ringwald (Martin); B. Rosen (Barry); N. Rosenthal (Nadia); J. Rossant (Janet); P. Ruiz Noppinger (Patricia); S. Ryder; J.Z. Schick (Joel Zupicich); F. Schnütgen (Frank); C.J. Schofield (Christopher); C. Seisenberger (Claudia); M. Selloum (Mohammed); E.M. Simpson (Elizabeth); W.C. Skarnes (William); D. Smedley (Damian); W.L. Stanford (William); A. Francis Stewart (A.); K. Stone (Kevin); K. Swan (Kate); H. Tadepally (Hamsa); J.L. Teboul (Jean Louis); G.P. Tocchini-Valentini (Glauco); D. Valenzuela (David); A.P. West (Anthony); K.-I. Yamamura (Ken-Ichi); Y. Yoshinaga (Yuko); M. Wurst (Martin)


    textabstractIn 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed highthroughput gene trapping and, i

  2. Systematic design of mouse Vh gene family-specific oligonucleotides

    Seijen, AM; Seijen, HG; Bos, NA


    Kabat's database has often been used to design mouse Vh gene-specific 5 ' primers. The emphasis was mostly on constructing a universal (degenerate) 5 ' primer or 5 ' primer set, which would be able to match every mouse Vh gene. We were interested in finding oligonucleotides that could be used as pri

  3. Phenylephrine-induced reversible cataract in the mouse.

    Claoué, C M


    Topical 10% phenylephrine will produce lens opacities in several strains of mouse. These lens opacities resolve spontaneously within 24 hours, leaving an apparently normal eye. Phenylephrine-induced lens opacification in the mouse can be prevented by covering the eye with ointment, suggesting that the underlying mechanism is transcorneal dehydration.

  4. Urinary virulence of Proteus mirabilis in two experimental mouse models.

    Peerbooms, P G; Marian, A.; Verweij, J. J.; MacLaren, D. M.


    Two experimental mouse models were tested for their suitability in measuring urinary virulence of Proteus mirabilis. In the first model, the kidney-infecting dose and lethal dose were measured. In the second model, the kinetics of the numbers of bacteria in the kidneys and other organs of the mouse were monitored for 13 h after injection.

  5. Designing Mouse Behavioral Tasks Relevant to Autistic-Like Behaviors

    Crawley, Jacqueline N.


    The importance of genetic factors in autism has prompted the development of mutant mouse models to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (1) face validity, i.e., resemblance to the human symptoms; (2) construct validity, i.e.,…

  6. Radioimmunodetection of human choriocarcinoma xenograft in nude mouse


    Objective: To study the efficiency of radioimmuno-detection in locating the xenograft of human chorio-carcinoma in nude mouse. Methods: Radioimmuno-detection was performed using cocktail antibodies of 131I-labeled mouse anti-human chorionic gonadotropin monoclonal antibodies to locate the xenograft of human choriocarcinoma in nude mouse. Radioactivity in different tissues was measured and the tumor/non-tumor ratio was calculated. Normal mouse IgG was used as control IgG. Results: The accumulation of radioactivity in the xenograft area could be recognized as early as 24 h after the injection of the radiolabelled antibodies. 72-96 h after the injection, the xenograft could be clearly shown. The minimal shown xenograft was 0.8 cm in diameter. The tumor/non-tumor ratio increased with the time and was obviously higher than that in control group. Conclusion: Radioimmunodetection can efficiently locate human choriocarcinoma xenograft in nude mouse.

  7. Immunologic analyses of mouse cystathionase in normal and leukemic cells

    Rabbit antisera have been raised against mouse liver cystathionase and shown to possess enzyme neutralizing activity. Agar gel double immunodiffusion analyses demonstrated that both mouse liver cystathionase and rat liver cystathionase react with the antisera, the latter enzyme being completely cross-reactive with the former. Following radioiodination of the purified rat liver enzyme, a double antibody radioimmunoassay was developed in which greater than 90% of the labeled protein could be specifically precipitated with the anti-mouse cystathionase antibodies. In this test the purified rat liver and mouse liver enzymes were virtually indistinguishable, generating superimposable competition displacement curves on a protein mass basis. These results indicate that both enzymes are immunologically identical, thus validating the use of the rat in lieu of the murine liver enzyme as radiolabeled tracer in an assay for mouse cystathionase. In addition, competition radioimmunoassays demonstrated that the immunological reactivities of both the purified rat liver and mouse liver enzymes were equally heat sensitive. The sensitivity of the assay was determined to be 1 ng of enzyme protein/0.22 mL of assay mixture, and the assay could be used to detect the presence of enzyme protein in tissue homogenates of single mouse organs. Mouse or rat cross-reactivity with human liver cystathionase was incomplete; but, with the exception of heart and spleen, parallel radioimmunoassay competition displacement curves were obtained for cystathionase from different mouse organs including thymus. Extracts of 7-, 9-, and 10-month-old spontaneous AKR mouse thymomas were tested in the radioimmunoassay along with extracts of age-matched thymuses which were grossly tumor free. A reaction of nonidentity was observed for all of the tumor extracts while a reaction identical with that of the pure liver enzyme was found with all of the normal thymus extracts

  8. The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009

    Russell, Liane B [ORNL


    The large mouse genetics program at the Oak Ridge National Lab is often re-membered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-Chromosome s importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a valuable

  9. Mouse Hematopoietic Stem Cells, Unlike Human and Mouse Embryonic Stem Cells, Exhibit Checkpoint–Apoptosis Coupling

    Rohrabaugh, Sara; Mantel, Charlie; Broxmeyer, Hal E.


    Previously, we reported that the spindle assembly checkpoint (SAC), which is coupled in somatic cells, is uncoupled from apoptosis-initiation in mouse and human embryonic stem cells (ESCs). This condition allows ESCs to tolerate and proliferate as polyploidy/aneuploid cells. Proper function of the SAC is vital to prevent polyploidy/aneuploidy during ex vivo hematopoietic stem cell (HSC) expansion. Here we address, for the first time, whether HSCs are more like ESCs or somatic cells with respe...

  10. A Transgenic Mouse Model of Poliomyelitis.

    Koike, Satoshi; Nagata, Noriyo


    Transgenic mice (tg mice) that express the human poliovirus receptor (PVR), CD155, are susceptible to poliovirus and develop a neurological disease that resembles human poliomyelitis. Assessment of the neurovirulence levels of poliovirus strains, including mutant viruses produced by reverse genetics, circulating vaccine-derived poliovirus, and vaccine candidates, is useful for basic research of poliovirus pathogenicity, the surveillance of circulating polioviruses, and the quality control of oral live poliovirus vaccines, and does not require the use of monkeys. Furthermore, PVR-tg mice are useful for studying poliovirus tissue tropism and host immune responses. PVR-tg mice can be bred with mice deficient in the genes involved in viral pathogenicity. This report describes the methods used to analyze the pathogenicity and immune responses of poliovirus using the PVR-tg mouse model. PMID:26983733

  11. A mouse model for testing remyelinating therapies.

    Bai, C Brian; Sun, Sunny; Roholt, Andrew; Benson, Emily; Edberg, Dale; Medicetty, Satish; Dutta, Ranjan; Kidd, Grahame; Macklin, Wendy B; Trapp, Bruce


    Used in combination with immunomodulatory therapies, remyelinating therapies are a viable therapeutic approach for treating individuals with multiple sclerosis. Studies of postmortem MS brains identified greater remyelination in demyelinated cerebral cortex than in demyelinated brain white matter and implicated reactive astrocytes as an inhibitor of white matter remyelination. An animal model that recapitulates these phenotypes would benefit the development of remyelination therapeutics. We have used a modified cuprizone protocol that causes a consistent and robust demyelination of mouse white matter and cerebral cortex. Spontaneous remyelination occurred significantly faster in the cerebral cortex than in white matter and reactive astrocytes were more abundant in white matter lesions. Remyelination of white matter and cerebral cortex was therapeutically enhanced by daily injections of thyroid hormone triiodothyronine (T3). In summary, we describe an in vivo demyelination/remyelination paradigm that can be powered to determine efficacy of therapies that enhance white matter and cortical remyelination. PMID:27384502

  12. Circadian oscillators in the mouse brain

    Rath, Martin F; Rovsing, Louise; Møller, Morten


    The circadian timekeeper of the mammalian brain resides in the suprachiasmatic nucleus of the hypothalamus (SCN), and is characterized by rhythmic expression of a set of clock genes with specific 24-h daily profiles. An increasing amount of data suggests that additional circadian oscillators...... residing outside the SCN have the capacity to generate peripheral circadian rhythms. We have recently shown the presence of SCN-controlled oscillators in the neocortex and cerebellum of the rat. The function of these peripheral brain clocks is unknown, and elucidating this could involve mice with...... conditional cell-specific clock gene deletions. This prompted us to analyze the molecular clockwork of the mouse neocortex and cerebellum in detail. Here, by use of in situ hybridization and quantitative RT-PCR, we show that clock genes are expressed in all six layers of the neocortex and the Purkinje and...

  13. Tissue morphodynamics shaping the early mouse embryo.

    Sutherland, Ann E


    Generation of the elongated vertebrate body plan from the initially radially symmetrical embryo requires comprehensive changes to tissue form. These shape changes are generated by specific underlying cell behaviors, coordinated in time and space. Major principles and also specifics are emerging, from studies in many model systems, of the cell and physical biology of how region-specific cell behaviors produce regional tissue morphogenesis, and how these, in turn, are integrated at the level of the embryo. New technical approaches have made it possible more recently, to examine the morphogenesis of the mouse embryo in depth, and to elucidate the underlying cellular mechanisms. This review focuses on recent advances in understanding the cellular basis for the early fundamental events that establish the basic form of the embryo. PMID:26820524

  14. Insights from Human/Mouse genome comparisons

    Pennacchio, Len A.


    Large-scale public genomic sequencing efforts have provided a wealth of vertebrate sequence data poised to provide insights into mammalian biology. These include deep genomic sequence coverage of human, mouse, rat, zebrafish, and two pufferfish (Fugu rubripes and Tetraodon nigroviridis) (Aparicio et al. 2002; Lander et al. 2001; Venter et al. 2001; Waterston et al. 2002). In addition, a high-priority has been placed on determining the genomic sequence of chimpanzee, dog, cow, frog, and chicken (Boguski 2002). While only recently available, whole genome sequence data have provided the unique opportunity to globally compare complete genome contents. Furthermore, the shared evolutionary ancestry of vertebrate species has allowed the development of comparative genomic approaches to identify ancient conserved sequences with functionality. Accordingly, this review focuses on the initial comparison of available mammalian genomes and describes various insights derived from such analysis.

  15. Characterization of individual mouse cerebrospinal fluid proteomes

    Smith, Jeffrey S.; Angel, Thomas E.; Chavkin, Charles; Orton, Daniel J.; Moore, Ronald J.; Smith, Richard D.


    Analysis of cerebrospinal fluid (CSF) offers key insight into the status of the central nervous system. Characterization of murine CSF proteomes can provide a valuable resource for studying central nervous system injury and disease in animal models. However, the small volume of CSF in mice has thus far limited individual mouse proteome characterization. Through non-terminal CSF extractions in C57Bl/6 mice and high-resolution liquid chromatography-mass spectrometry analysis of individual murine samples, we report the most comprehensive proteome characterization of individual murine CSF to date. Utilizing stringent protein inclusion criteria that required the identification of at least two unique peptides (1% false discovery rate at the peptide level) we identified a total of 566 unique proteins, including 128 proteins from three individual CSF samples that have been previously identified in brain tissue. Our methods and analysis provide a mechanism for individual murine CSF proteome analysis.

  16. Candida albicans escapes from mouse neutrophils

    Ermert, David; Niemiec, Maria J; Röhm, Marc;


    Candida albicans, the most commonly isolated human fungal pathogen, is able to grow as budding yeasts or filamentous forms, such as hyphae. The ability to switch morphology has been attributed a crucial role for the pathogenesis of C. albicans. To mimic disseminated candidiasis in humans, the mouse...... is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We...... revealed that murine neutrophils exhibited a significantly lower ability to kill C. albicans than their human counterparts. Strikingly, C. albicans yeast cells formed germ tubes upon internalization by murine neutrophils, eventually rupturing the neutrophil membrane and thereby, killing the phagocyte. On...

  17. Mouse models of intestinal inflammation and cancer.

    Westbrook, Aya M; Szakmary, Akos; Schiestl, Robert H


    Chronic inflammation is strongly associated with approximately one-fifth of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here, we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With

  18. The functional landscape of mouse gene expression

    Zhang Wen


    Full Text Available Abstract Background Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. Results We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. Conclusions We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.

  19. Effect of Duplicate Genes on Mouse Genetic Robustness: An Update

    Zhixi Su


    Full Text Available In contrast to S. cerevisiae and C. elegans, analyses based on the current knockout (KO mouse phenotypes led to the conclusion that duplicate genes had almost no role in mouse genetic robustness. It has been suggested that the bias of mouse KO database toward ancient duplicates may possibly cause this knockout duplicate puzzle, that is, a very similar proportion of essential genes (PE between duplicate genes and singletons. In this paper, we conducted an extensive and careful analysis for the mouse KO phenotype data and corroborated a strong effect of duplicate genes on mouse genetics robustness. Moreover, the effect of duplicate genes on mouse genetic robustness is duplication-age dependent, which holds after ruling out the potential confounding effect from coding-sequence conservation, protein-protein connectivity, functional bias, or the bias of duplicates generated by whole genome duplication (WGD. Our findings suggest that two factors, the sampling bias toward ancient duplicates and very ancient duplicates with a proportion of essential genes higher than that of singletons, have caused the mouse knockout duplicate puzzle; meanwhile, the effect of genetic buffering may be correlated with sequence conservation as well as protein-protein interactivity.

  20. Chromosomal localization of the human and mouse hyaluronan synthase genes

    Spicer, A.P.; McDonald, J.A. [Mayo Clinic Scottsdale, AZ (United States); Seldin, M.F. [Univ. of California Davis, CA (United States)] [and others


    We have recently identified a new vertebrate gene family encoding putative hyaluronan (HA) synthases. Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse. All three genes encode predicted plasma membrane proteins with multiple transmembrane domains and approximately 25% amino acid sequence identity to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any one HAS gene in transfected mammalian cells leads to high levels of HA biosynthesis. We now report the chromosomal localization of the three HAS genes in human and in mouse. The genes localized to three different positions within both the human and the mouse genomes. HAS1 was localized to the human chromosome 19q13.3-q13.4 boundary and Has1 to mouse Chr 17. HAS2 was localized to human chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces the recently reported relationship between a small region of human chromosome 19q and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical region delineated for the Langer-Giedion syndrome and can thus be excluded as a candidate gene for this genetic syndrome. 33 refs., 2 figs.

  1. Cloning and sequencing of mouse GABA transporter complementary DNA



    A cDNA encoding the mouse GABA transporter has been isolated and sequenced.The results show that the mouse GABA transporter cDNA differs from that of the rat by 60 base pairs at the open reading frame region but the deduced amino acid sequences of the two cDNAs are identical and both composed of 599 amino acids.However,the amino acid sequence is different from the sequence deduced from a recently published mouse GABA transporter cDNA.

  2. 网络口碑 Word of mouse


    英文里“word of mouth”意思是“口碑”,但是大家听说过“word of mouse”吗?这两个短语有什么关系呢?Word of mouse is an electronic version of the time—tested idea of WOrd of mouth. Numerous advertisers have jumped on the word of mouse bandwagon using a variety of innovative techniques to get their message out to consumers,and businesses all over the world rely on word of mouse to promote good reputations.

  3. Chimeric elk/mouse prion proteins in transgenic mice

    Tamguney, G; Giles, K; Oehler, A.; Johnson, NL; DeArmond, SJ; Prusiner, SB


    Chronic wasting disease (CWD) of deer and elk is a highly communicable neurodegenerative disorder caused by prions. Investigations of CWD are hampered by slow bioassays in transgenic (Tg) mice. Towards the development of Tg mice that will be more susceptible to CWD prions, we created a series of chimeric elk/mouse transgenes that encode the N terminus of elk PrP (ElkPrP) up to residue Y168 and the C terminus of mouse PrP (MoPrP) beyond residue 169 (mouse numbering), designated Elk3M(SNIVVK). ...

  4. Meeting Report: The Twelfth International Mouse Genome Conference

    Manolakou, Katerina; Cross, Sally H.; Simpson, Eleanor H.; Jackson, Ian J.


    The annual International Mouse Genome Conference (IMGC) is where, scientifically speaking, classical mouse genetics meets the relative newcomer of genomics. The 12th meeting took place last October in the delightful Bavarian village of Garmisch-Partenkirchen, and we were greeted by the sight on the mountains of the first snowfall of the season. However the discussions left little time for exploration. Minds of participants in Garmisch were focused by a recent document produced by the NIH and by discussions within other funding agencies worldwide. If implemented, the proposals will further enhance the status of the mouse as the principal model for study of the function of the human genome.

  5. Differentially expressed genes in repairing irradiation-induced damage in mouse intestinal tract by foreign mouse small intestinal RNA

    To study the differentially expressed genes correlative to irradiation-induced damage in mouse intestinal tract and its repair by foreign mouse small intestinal RNA. Divide 90 mice into 4 groups randomly. For the experimental groups, each mouse was given 40μg foreign mouse small intestinal RNA, and for the control groups, 0.4 mL of 0.9% NaCl. The intestinal specimens were collected form each group 6h, 12h, 24h, 4d and 8d after 60Co γ-rays irradiation respectively. The differentially expressed genes in the tested and control groups were checked and cloned by long-distance PCR based on subtractive hybridization. 165 differential gene clones were obtained, of which 75 named as AXCZI-75 maybe were correlated with the irradiation-induced damage in mouse intestinal tract; and 90 named as XCZ1-90 maybe were correlated with repairing of the damaged mouse intestinal tract by foreign mouse small intestinal RNA

  6. Mouse Study Offers Hope for Vaccine Against Chlamydia

    ... page: Mouse Study Offers Hope for Vaccine Against Chlamydia Bacteria's ... 2016 (HealthDay News) -- A new Canadian study with mice suggests there is hope for a vaccine to ...

  7. Children’s Comedy —The Mouse Wedding


    During the coming winter vacation, a new children’s comedy entitled The Mouse Wedding will be per- formed by the Beijing Dingshang Culture Co. Ltd. at the PLA Theater. We warmly welcome children three to 10 years

  8. Preble's Meadow Jumping Mouse Critical Habitat Streams Proposed 2009

    US Fish and Wildlife Service, Department of the Interior — This data corresponds tp a proposed revision to the amount of critical habitat designated for the Preble's meadow jumping mouse in Colorado where it is listed as a...

  9. Conservation and the ecology of the Salt Marsh Harvest Mouse

    US Fish and Wildlife Service, Department of the Interior — This article describes the habitat, population, and behavior of the endangered Salt Marsh Harvest Mouse. The recovery plan for this species is also discussed.

  10. Interactive Mouse-Driven Animation of Mathematical Processes.

    Greenleaf, Newcomb


    Provides examples from elementary mathematics principles which illustrate some of the advantages of an interactive mouse-driven animation. Explains the effectiveness of this approach with exercises dealing with a plane of waves and quadratic formulas. (ML)

  11. Mouse Experimental Myopia Has Features of Primate Myopia

    Tkatchenko, Tatiana V.; Shen, Yimin; Tkatchenko, Andrei V.


    High-resolution MRI analysis of mouse experimental myopia revealed that the development of myopia in mice is attributed to axial elongation of the vitreous chamber of the eye, as in humans and nonhuman primates.

  12. Predictably irrational: assaying cognitive inflexibility in mouse models of schizophrenia

    Jonathan L Brigman


    Full Text Available The development of sophisticated, translatable mouse-based assays modeling the behavioral manifestations of neuropsychiatric diseases such as schizophrenia has lagged the advances in molecular and genomic techniques. Our laboratory has made efforts to fill this gap by investing in the development of novel assays, including adapting a touchscreen-based method for measuring cognitive and executive functions for use in mice. As part of these efforts, a recent study by Brigman et al. (2009 investigated the effects of subchronic phencyclidine (PCP treatment on mouse touchscreen-based pairwise visual discrimination and reversal learning. Here, we summarize the results of that study and place them in the larger context of ongoing efforts to develop valid mouse ‘models’ of schizophrenia, with a focus on reversal learning and other measures of cognitive flexibility. Touchscreen-based systems could provide a tractable platform for fully utilizing the mouse to elucidate the pathophysiology of cognitive inflexibility in schizophrenia and other neuropsychiatric disorders.

  13. An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man

    Ravasi, Timothy


    Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

  14. Mouse Karyotype Obtained by Combining DAPI Staining with Image Analysis


    In this study, mitotic metaphase chromosomes in mouse were identified by a new chromosome fluorescence banding technique combining DAPI staining with image analysis. Clear 4', 6-diamidino-2-phenylindole (DAPI) multiple bands like G-bands could be produced in mouse. The MetaMorph software was then used to generate linescans of pixel intensity for the banded chromosomes from short arm to long arm. These linescans were sufficient not only to identify each individual chromosome but also analyze the physical sites of bands in chromosome. Based on the results, the clear and accurate karyotype of mouse metaphase chromosomes was established. The technique is therefore considered to be a new method for cytological studies of mouse.

  15. The similarity of gene expression between human and mouse tissues

    Dowell, Robin D.


    Meta-analysis of human and mouse microarray data reveals conservation of patterns of gene expression that will help to better characterize the evolution of gene expression. See research article:

  16. Human · mouse genome analysis and radiation biology. Proceedings

    This issue is the collection of the papers presented at the 25th NIRS symposium on Human, Mouse Genome Analysis and Radiation Biology. The 14 of the presented papers are indexed individually. (J.P.N.)

  17. Effects of UVC-irradiation on cultured mouse embryonic cells

    Effects of UVC-irradiation on the cultured differentiating mouse embryonic cells were investigated. Embryonic mesenchymal cells, isolated from fore-and hind-limbs or mid brain of Day 11 mouse embryos, and 3T3 cells, a reference mouse fibroblast cell line, were irradiated with UVC at a dose range of 0∼30 J/m2. Dose-dependent inhibition was found for both cellular proliferation and differentiation, dose-dependent induction of DNA cyclobutane pyrimidine dimers and (6-4) photoproducts were found in the embryonic cells. Mesenchymal chondrogenesis was more sensitive to the UVC than proliferation, and the UVC-induced DNA damage and their repair kinetics in the cultured embryonic cells were similar to those in mouse 3T3 cells. No effects of treatments by the fluorescent light pre or post UVC-irradiation were found on the repair kinetics of DNA damage in all of the cells

  18. Glycoconjugates Distribution during Developing Mouse Spinal Cord Motor Organizers

    Vojoudi, Elham; Ebrahimi, Vahid; Ebrahimzadeh-Bideskan, Alireza; Fazel, Alireza


    Background: The aim of this research was to study the distribution and changes of glycoconjugates particularly their terminal sugars by using lectin histochemistry during mouse spinal cord development. Methods: Formalin-fixed sections of mouse embryo (10-16 fetal days) were processed for lectin histochemical method. In this study, two groups of horseradish peroxidase -labeled specific lectins were used: N-acetylgalactosamine, including Dolichos biflorus, Wisteria floribunda agglutinin (WFA), ...

  19. "The Lion and the Mouse"教学案例



    @@ 一、教学内容(Teaching content) There is a lion. He is big. He is very strong. His teeth are big and sharp. This is a mouse. She is small. Her teeth are small and sharp. The lion is hungryv. The mouse is afraid, "Don't eat me,please." Oh! The lion is in the net! He is very afraid, "Help! Help! Who can help me?"

  20. Mouse Models for Studying the Formation and Propagation of Prions*

    Watts, JC; Prusiner, SB


    Prions are self-propagating protein conformers that cause a variety of neurodegenerative disorders in humans and animals. Mouse models have played key roles in deciphering the biology of prions and in assessing candidate therapeutics. The development of transgenic mice that form prions spontaneously in the brain has advanced our understanding of sporadic and genetic prion diseases. Furthermore, the realization that many proteins can become prions has necessitated the development of mouse mode...

  1. Mouse Control using a Web Camera based on Colour Detection


    In this paper we present an approach for Human computer Interaction (HCI), where we have tried to control the mouse cursor movement and click events of the mouse using hand gestures. Hand gestures were acquired using a camera based on colour detection technique. This method mainly focuses on the use of a Web Camera to develop a virtual human computer interaction device in a cost effective manner.

  2. Isolation, purification, and characterization of mouse placental lactogen.

    Colosi, P; Marr, G; Lopez, J; Haro, L; Ogren, L; Talamantes, F


    Mouse placental lactogen was purified 1840-fold from BALB/c placentae from days 14-18 of gestation with an overall yield of 29%. The purification procedure included alkaline homogenization and extraction, ammonium sulfate precipitation, hydrophobic interaction chromatography on Phenyl-Sepharose, ion-exchange chromatography on CM- and DEAE-cellulose, and gel exclusion chromatography on Sephadex G-100. On 10% alkaline polyacrylamide gels, mouse placental lactogen had an Rf of 0.19. Electrophore...

  3. Mouse Mutagenesis Using N-Ethyl-N-Nitrosourea (ENU)



    Authors: Andrew P. Salinger and Monica J. Justice1 Corresponding author ([]()) ### INTRODUCTION This protocol describes chemical mutagenesis of male mice using N-ethyl-N-nitrosourea (ENU), which is the most efficient method for obtaining mouse mutations in phenotype-driven screens. A fractionated dose of ENU, an alkylating agent, can produce a mutation rate as high as 1.5 × 10e−3 in male mouse spermatogonial stem cells. Treatment with ENU pr...

  4. Computerized Assessment of Social Approach Behavior in Mouse

    Page, Damon T.; Kuti, Orsolya J.


    Altered sociability is a core feature of a variety of human neurological disorders, including autism. Social behaviors may be tested in animal models, such as mice, to study the biological basis of sociability and how this is altered in neurodevelopmental disorders. A quantifiable social behavior frequently used to assess sociability in the mouse is the tendency to approach and interact with an unfamiliar mouse. Here we present a novel computer-assisted method for scoring social approach beha...

  5. Mouse Genome Editing using CRISPR/Cas System

    Harms, Donald W.; Quadros, Rolen M; Seruggia, Davide; Ohtsuka, Masato; Takahashi, Gou; Montoliu, Lluis; Gurumurthy, Channabasavaiah B


    The availability of techniques to create desired genetic mutations has enabled the laboratory mouse as an extensively used model organism in biomedical research including human genetics. A new addition to this existing technical repertoire is the CRISPR/Cas system. Specifically, this system allows editing of the mouse genome much faster than the previously used techniques and more importantly multiple mutations can be created in a single experiment. Here we provide protocols for preparation o...

  6. Mouse Tumor Biology Database (MTB): enhancements and current status

    Bult, Carol J.; Krupke, Debra M.; Sundberg, John P.; Eppig, Janan T.


    The Mouse Tumor Biology Database (MTB) is a Web-based resource that provides access to information on tumor frequency and latency, genetics and pathology in genetically defined mice (transgenics, targeted mutations and inbred strains). MTB is designed to serve as an information resource for cancer genetics researchers who use the laboratory mouse as a model system for understanding human disease processes. Data in MTB are obtained from the primary scientific literature and direct submissions ...

  7. End Sequencing and Finger Printing of Human & Mouse BAC Libraries

    Fraser, C


    This project provided for continued end sequencing of existing and new BAC libraries constructed to support human sequencing as well as to initiate BAC end sequencing from the mouse BAC libraries constructed to support mouse sequencing. The clones, the sequences, and the fingerprints are now an available resource for the community at large. Research and development of new metaodologies for BAC end sequencing have reduced costs and increase throughput.

  8. Anatomical Origins of Ocular Dominance in Mouse Primary Visual Cortex

    Coleman, Jason E.; Law, Karen; Bear, Mark F.


    Ocular dominance (OD) plasticity is a classic paradigm for studying the effect of experience and deprivation on cortical development, and is manifested as shifts in the relative strength of binocular inputs to primary visual cortex (V1). The mouse has become an increasingly popular model for mechanistic studies of OD plasticity and, consequently, it is important that we understand how binocularity is constructed in this species. One puzzling feature of the mouse visual system is the gross dis...

  9. Transgenic mouse model for the study of enterovirus 71 neuropathogenesis

    Fujii, Ken; Nagata, Noriyo; Sato, Yuko; Ong, Kien Chai; Wong, Kum Thong; Yamayoshi, Seiya; Shimanuki, Midori; Shitara, Hiroshi; Taya, Choji; KOIKE, Satoshi


    EV71 infection with severe neurological complications has become a serious public health concern. However, suitable small animal models to study human EV71 pathogenesis are not available. We have generated a Tg mouse model by expressing the human EV71 receptor, Scavenger receptor B2, and found it to be susceptible to EV71 infection. This Tg mouse model exhibits neurological disease and pathology very similar to that observed in humans. The results confirm that the Scavenger receptor B2 recept...

  10. Barrier Qualities of the Mouse Eye to Topically Applied Drugs

    Wang, Zhao; Do, Chi Wai; Avila, Marcel Y.; Stone, Richard A.; Jacobson, Kenneth A.; Civan, Mortimer M.


    The mouse eye displays unusually rapid intraocular pressure (IOP) responses to topically applied drugs as measured by the invasive servo-null micropipette system (SNMS). To learn if the time course reflected rapid drug transfer across the thin mouse cornea and sclera, we monitored a different parameter, pupillary size, following topical application of droplets containing 40 μM (0.073μg) carbachol. No miosis developed from this low carbachol concentration unless the cornea was impaled with an ...

  11. A Consensus Definition of Cataplexy in Mouse Models of Narcolepsy

    Scammell, Thomas E.; Willie, Jon T.; Guilleminault, Christian; Siegel, Jerome M.


    People with narcolepsy often have episodes of cataplexy, brief periods of muscle weakness triggered by strong emotions. Many researchers are now studying mouse models of narcolepsy, but definitions of cataplexy-like behavior in mice differ across labs. To establish a common language, the International Working Group on Rodent Models of Narcolepsy reviewed the literature on cataplexy in people with narcolepsy and in dog and mouse models of narcolepsy and then developed a consensus definition of...

  12. Mouse Mos protooncogene product is present and functions during oogenesis.

    Paules, R S; Buccione, R; Moschel, R C; Vande Woude, G F; Eppig, J.J.


    We have identified the mouse Mos-encoded protein product, p39mos, in maturing mouse oocytes and have shown that it is indistinguishable from the product expressed in Mos-transformed NIH 3T3 cells. p39mos is detected in oocytes arrested in the first meiotic prophase, during germinal-vesicle breakdown, metaphase I, anaphase I, and in ovulated eggs. We show that microinjection of three different Mos antisense (but not sense) oligodeoxyribonucleotides into germinal vesicle-stage oocytes prevents ...

  13. Rapid genetic algorithm optimization of a mouse computational model: Benefits for anthropomorphization of neonatal mouse cardiomyocytes

    Corina Teodora Bot


    Full Text Available While the mouse presents an invaluable experimental model organism in biology, its usefulness in cardiac arrhythmia research is limited in some aspects due to major electrophysiological differences between murine and human action potentials (APs. As previously described, these species-specific traits can be partly overcome by application of a cell-type transforming clamp (CTC to anthropomorphize the murine cardiac AP. CTC is a hybrid experimental-computational dynamic clamp technique, in which a computationally calculated time-dependent current is inserted into a cell in real time, to compensate for the differences between sarcolemmal currents of that cell (e.g., murine and the desired species (e.g., human. For effective CTC performance, mismatch between the measured cell and a mathematical model used to mimic the measured AP must be minimal. We have developed a genetic algorithm (GA approach that rapidly tunes a mathematical model to reproduce the AP of the murine cardiac myocyte under study. Compared to a prior implementation that used a template-based model selection approach, we show that GA optimization to a cell-specific model results in a much better recapitulation of the desired AP morphology with CTC. This improvement was more pronounced when anthropomorphizing neonatal mouse cardiomyocytes to human-like APs than to guinea pig APs. CTC may be useful for a wide range of applications, from screening effects of pharmaceutical compounds on ion channel activity, to exploring variations in the mouse or human genome. Rapid GA optimization of a cell-specific mathematical model improves CTC performance and may therefore expand the applicability and usage of the CTC technique.

  14. Characterization of the mouse pancreatic islet proteome and comparative analysis with other mouse tissues

    Petyuk, Vladislav A.; Qian, Weijun; Hinault, Charlotte; Gritsenko, Marina A.; Singhal, Mudita; Monroe, Matthew E.; Camp, David G.; Kulkarni, Rohit N.; Smith, Richard D.


    The pancreatic islets of Langerhans and insulin-producing beta cells in particular play a central role in the maintenance of glucose homeostasis and the islet dysfunction is associated with the pathogenesis of both type 1 and type 2 diabetes mellitus. To contribute to the understanding of the biology of the pancreatic islets we applied proteomic techniques based on liquid chromatography coupled with mass spectrometry. Here as an initial step we present the first comprehensive proteomic characterization of pancreas islets of the mouse, the commonly used animal model for diabetes research. Two-dimensional SCX LC/RP LC-MS/MS has been applied to characterize of the mouse islet proteome, resulting in the confident identification of 17,350 different tryptic peptides covering 2,612 proteins with at least two unique peptide identifications per protein. The dataset also allowed identification of a number of post-translational modifications including several modifications relevant to oxidative stress and phosphorylation. While many of the identified phosphorylation sites corroborates with previous known sites, the oxidative modifications observed on cysteinyl residues potentially reveal novel information related to the role of oxidation stress in islet functions. Comparative analysis of the islet proteome database with 15 available proteomic datasets from other mouse tissues and cells revealed a set of 68 proteins uniquely detected only in the pancreatic islets. Besides proteins with known functions, like islet secreted peptide hormones, this unique set contains a number of proteins with yet unknown functions. The resulting peptide and protein database will be available at web site of the NCRR proteomic center (

  15. Characterization of mouse Clpp protease cDNA, gene, and protein

    Andresen, B S; Corydon, T J; Wilsbech, M;


    characterized the mouse Clpp cDNA sequence, the organization of the mouse gene, the chromosomal localization, and the tissue-specific expression pattern. Moreover. the cellular localization and processing of mouse Clpp was studied by overexpression in transfected eukaryotic cells. Our results indicate that...... mouse and human Clpp have similar roles, and they provide the molecular basis for establishing a Clpp knockout mouse and to study its phenotype, thereby shedding light on a possible role of Clpp in human disease....

  16. Virtues and limitations of the preimplantation mouse embryo as a model system

    Robert A Taft


    The mouse is the most widely used model of preimplantation embryo development, but is it a good model? Its small size, prolificacy and ease of handling make the mouse a relatively low cost, readily available and attractive alternative when embryos from other species are difficult or expensive to obtain. However, the real power of the mouse as a model lies in mouse genetics. The development of inbred mouse strains facilitated gene discovery as well as our understanding of gene function and reg...

  17. Human and mouse mitochondrial orthologs of bacterial ClpX

    Corydon, T J; Wilsbech, M; Jespersgaard, C;


    mapping placing the CLPX gene 4.6 cR distal to D15S159. Murine ClpX cDNA was sequenced, and the mouse Clpx locus was mapped to a position between 31 and 42 cM offset from the centromere on mouse Chr 9. Experimental observations indicate the presence of a pseudogene in the mouse genome and sequence...... variability between mouse ClpX cDNAs from different strains. Alignment of the human and mouse ClpX amino acid sequences with ClpX sequences from other organisms shows that they display the typical modular organization of domains with one AAA(+) domain common to a large group of ATPases and several other...... domains conserved in ClpX orthologs linked by non-conserved sequences. Notably, a C-4 zinc finger type motif is recognized in human and mouse ClpX. This motif of so far unknown function is present only in a subset of the known ClpX sequences....

  18. Mouse models to study dengue virus immunology and pathogenesis

    Raphaël M. Zellweger


    Full Text Available The development of a compelling murine model of dengue virus (DENV infection has been challenging, because dengue virus clinical isolates do not readily replicate or cause pathology in immunocompetent mice. However, research using immunocompromised mice and/or mouse-adapted viruses allows to investigate questions that may be impossible to address in human studies. In this review, we discuss the potential strengths and limitations of existing mouse models of dengue disease. Human studies are descriptive by nature; moreover, the strain, time, and sequence of infection are often unknown. In contrast, in mice, the conditions of infection are well defined and a large number of experimental parameters can be varied at will. Therefore, mouse models offer an opportunity to experimentally test hypotheses that are based on epidemiological observations. In particular, gain-of-function or loss-of-function models can be established to assess how different components of the immune system (either alone or in combination contribute to protection or pathogenesis during secondary infections or after vaccination. In addition, mouse models have been used for pre-clinical testing of antiviral drug or for vaccine development studies. Conclusions based on mouse experiments must be extrapolated to DENV infection in humans with caution due to the inherent limitations of animal models. However, research in mouse models is a useful complement to in vitro and epidemiological data, and may delineate new areas that deserve attention during future human studies.

  19. Mouse estrous cycle identification tool and images.

    Shannon L Byers

    Full Text Available The efficiency of producing timed pregnant or pseudopregnant mice can be increased by identifying those in proestrus or estrus. Visual observation of the vagina is the quickest method, requires no special equipment, and is best used when only proestrus or estrus stages need to be identified. Strain to strain differences, especially in coat color can make it difficult to determine the stage of the estrous cycle accurately by visual observation. Presented here are a series of images of the vaginal opening at each stage of the estrous cycle for 3 mouse strains of different coat colors: black (C57BL/6J, agouti (CByB6F1/J and albino (BALB/cByJ. When all 4 stages (proestrus, estrus, metestrus, and diestrus need to be identified, vaginal cytology is regarded as the most accurate method. An identification tool is presented to aid the user in determining the stage of estrous when using vaginal cytology. These images and descriptions are an excellent resource for learning how to determine the stage of the estrous cycle by visual observation or vaginal cytology.

  20. Computer simulations of the mouse spermatogenic cycle

    Debjit Ray


    Full Text Available The spermatogenic cycle describes the periodic development of germ cells in the testicular tissue. The temporal–spatial dynamics of the cycle highlight the unique, complex, and interdependent interaction between germ and somatic cells, and are the key to continual sperm production. Although understanding the spermatogenic cycle has important clinical relevance for male fertility and contraception, there are a number of experimental obstacles. For example, the lengthy process cannot be visualized through dynamic imaging, and the precise action of germ cells that leads to the emergence of testicular morphology remains uncharacterized. Here, we report an agent-based model that simulates the mouse spermatogenic cycle on a cross-section of the seminiferous tubule over a time scale of hours to years, while considering feedback regulation, mitotic and meiotic division, differentiation, apoptosis, and movement. The computer model is able to elaborate the germ cell dynamics in a time-lapse movie format, allowing us to trace individual cells as they change state and location. More importantly, the model provides mechanistic understanding of the fundamentals of male fertility, namely how testicular morphology and sperm production are achieved. By manipulating cellular behaviors either individually or collectively in silico, the model predicts causal events for the altered arrangement of germ cells upon genetic or environmental perturbations. This in silico platform can serve as an interactive tool to perform long-term simulation and to identify optimal approaches for infertility treatment and contraceptive development.

  1. Multistage chemical carcinogenesis in mouse skin

    Slaga, T.J.; Fischer, S.M.; Weeks, C.E.; Klein-Szanto, A.J.P.


    Skin tumors in mice can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a noncarcinogenic tumor promoter. The initiation phase requires only a single application of either a direct acting carcinogen or a procarcinogen which has to be metabolized before being active and is essentially an irreversible step which probably involves a somatic cell mutation. There is a good correlation between the skin tumor initiating activites of several polycyclic aromatic hydrocarbons (PAH) and their ability to bind covalently to epidermal DNA. Laboratory results suggest that bay region diol-epoxides are the ultimate carcinogenic form of PAH carcinogens. Potent inhibitors and stimulators of PAH tumor initiation appear to affect the level of the PAH diol-epoxide reacting with specific DNA bases. Reecent data suggests that the tumor promotion stage involves at least three important steps: (1) the induction of embryonic looking cells (dark cells) in adult epidermis; (2) an increased production of epidermal prostaglandins and polyamines; (3) sustained proliferation of dark cells. Retinoic acid specifically inhibits step two whereas the anti-inflammatory steriod fluocinolone acetonide is a potent inhibitor of steps one and three. The mechanism and the importance of a specific sequence for each step in chemical carcinogenesis in mouse skin are detailed.


    B. Nasrollahzadeh


    Full Text Available litis study is based on embryotoxic effects of ethanol on embryos and discussing the morphologic and hhtahtgic changes and defects an mouse. Tlie female animals were divided in three groups. Hie first group untreated as a control group but the second and third group received 10% and 20% solutions of ethanol respectively. Animals get use to certain level of ethanol solution and in the 10th day, the pregnancy period has been started. Then on the 19th day of gestation, the embryos were taken out from their mother's uterus and were examined for morphologic, histologic and skeletal disorders. In the first examination, the major defect was weight and length reduction in the second and third groups. these deffects, were severe in the second group in compare to third group that might be related to little consumption of the ethanol solution, due to bitter taste. In conclusion the teratogenic effect of alcohol on skeleton and joint is clear.

  3. Isolation of mouse cell proteoglycan mutants

    The sulfated proteoglycans on the surface of cultured mammalian cells have been implicated in a variety of phenomena. To obtain more direct evidence for the role of these molecules in specific cellular functions, they are isolating mutants that produce altered sulfated proteoglycans from a cloned line of Swiss mouse 3T3 cells. This cell type was selected because it exhibits contact inhibition of growth and there is extensive information on its' cell surface and extracellular proteoglycans and other glycoproteins. Cells were chemically mutagenized and subjected to one or more cycles of radiation suicide in the presence of 35S-sulfate. By replica plating, 150 clones, which appear to incorporate abnormal amounts of 35S-sulfate, have been selected. After recloning three times via the replica plating technique, the proteoglycans of 29 clones have thus far been analyzed. They have identified four clones which appear to make altered amounts of either cell surface heparan sulfate or chondroitin sulfate. The biochemical bases for the altered levels of the proteoglycans are under study. Of particular interest, however, is the fact that in this limited collection of mutants the chemical alterations correlate with specific altered cellular morphologies

  4. Experimental Study of Mouse Cytomegalovirus Infected Mice

    崔雯; 董永绥; 方峰


    Summary: In order to investigate the human cytomegalovirus (HCMV) infection, the mouse cytomegalovirus (MCMV) infected mice were experimentally studied. 6 to 8 week old female BALB/C mice with immunosuppression were selected to undergo the MCMV inoculations: intracranial inoculation and peritoneal inoculation. MCMV of the infected mice in various organs and tissues were detected by using β-gal staining and in situ nucleic acid hybridization assay. The pathological changes were observed in HE staining paraffin-embedded sections. It was found that all the MCMV infected mice showed the retardation of growth and development, and feather looseness. Both intracranial inoculation of 104 PFU viruses or peritoneal inoculation of 106 PFU viruses resulted in the pathological changes, to some extent, of various organs and tissues in the mice. The pathological changes in liver were consistent with the amount of β-gal staining positive cells, indicating the liver lesions were mainly caused by viral proliferation. It was also found that the viruses in the immunosuppressed mice subjected to intracranial inoculation could spread to whole body organs, while the viruses in the immunosuppressed mice subjected to intrapeitoneal inoculation couldn't spread to the brain, suggesting blood-brain barrier could prevent the virus from spreading to the brain.

  5. Arachidonic acid metabolism in cultured mouse keratinocytes

    The authors attempted to characterize the general features of arachidonate metabolism in cultured mouse keratinocytes. The cells labeled with [3H]arachidonate were stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), ionophore A23187, and fetal bovine serum (FBS). Common to the three substances, phosphatidylinositol, phosphatidylethanolamine, and phosphatidylcholine almost equally served as sources of arachidonate liberated by the action of phospholipase A2. The stimulation of phospholipase A2 action was observed in the order of A23187 greater than FBS greater than TPA. When stimulated by TPA or A23187, the radioactivity released into the extracellular medium was mostly found in prostaglandin (PG) E2. Formation of other PGs and hydroxyeicosatetraenoate (HETE) was extremely limited. In the case of stimulation by FBS, however, the released radioactivity was mainly associated with non-converted arachidonate. FBS also inhibited the TPA- and A23187-induced conversion of arachidonate to PGE2. Phospholipid degradation induced by the three stimulators was similarly dependent on extracellular Ca2+. The stimulation by FBS and A23187 was suppressed by calmodulin antagonists, though the effect of A23187 was much more sensitive to the antagonists when compared to that of FBS. The authors observed more than additive effects of the three stimulators when tested together

  6. Induced thermal resistance in the mouse ear

    The mouse ear (pinna) was used to investigate the effect of two hyperthermic treatments. Heating was by immersion in hot water at 43.50C. A single treatment of about 50 minutes was required to cause necrosis in 50% of the ears treated. When heat treatment was given in two equal fractions the total heating time had to be increased if the interval between fractions was greater than four hours. By 24 hours a total treatment of about 100 minutes was required, indicating almost complete recovery from the first heating. Priming treatments at 43.50C induced thermal resistance to a second heat treatment at 43.50C. Maximum resistance was observed one day after a 20 minute priming and two days after a 40 minute priming, when the heating time had to be increased to 120 minutes, an increase by a factor of 2.4. Shorter priming treatments induced less resistance, the minimum heating time to produce an effect being two minutes. In all cases the effect decreased during the next four to five days. These results indicate that the reduced response of tissues to fractionated hyperthermia is due both to the repair of sublethal heat damage and induction of thermal resistance. (author)

  7. Mouse infection models for space flight immunology

    Chapes, Stephen Keith; Ganta, Roman Reddy; Chapers, S. K. (Principal Investigator)


    Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.

  8. Dexamethasone increases the number of RNA polymerase II molecules transcribing integrated mouse mammary tumor virus DNA and flanking mouse sequences.

    Firzlaff, J M; Diggelmann, H


    In mouse Ltk- cells that were transfected with recombinant bacteriophage DNA containing a complete proviral copy of an integrated endogenous mouse mammary tumor virus (MMTV) with its flanking cellular sequences, the newly acquired MMTV proviruses were transcribed in a glucocorticoid-responsive fashion. After hormone treatment of selected cell clones in culture we isolated the nuclei, elongated the nascent RNA chains in vitro, and determined the number of RNA polymerase II molecules on the tra...


    Metz, Richard P.; Qu, Xiaoyu; Laffin, Brian; Earnest, David; Porter, Weston W.


    Mouse mammary epithelial cells (HC-11) and mammary tissues were analyzed for developmental changes in circadian clock, cellular proliferation and differentiation marker genes. Expression of the clock genes, Per1 and Bmal1, were elevated in differentiated HC-11 cells whereas Per2 mRNA levels were higher in undifferentiated cells. This differentiation-dependent profile of clock gene expression was consistent with that observed in mouse mammary glands as Per1 and Bmal1 mRNA levels were elevated ...

  10. The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues.

    Croop, J M; Raymond, M; Haber, D; Devault, A; Arceci, R. J.; Gros, P.; Housman, D.E.


    The gene responsible for multidrug resistance (mdr), which encodes the P-glycoprotein, is a member of a multigene family. We have identified distinct mdr gene transcripts encoded by three separate mdr genes in the mouse. Expression levels of each mdr gene are dramatically different in various mouse tissues. Specific mdr RNA transcripts of approximately 4.5, 5, and 6 kilobases have been detected. Each of the mdr genes has a specific RNA transcript pattern. These results should be considered in...

  11. MR images of mouse brain using clinical 3T MR scanner and 4CH-Mouse coil

    Lim, Soo Mee; Park, Eun Mi; Lyoo, In Kyoon; Lee, Junghyun; Han, Bo Mi; Lee, Jeong Kyong; Lee, Su Bin


    Objectives: Although small-bore high-field magnets are useful for research in small rodent models,this technology, however, has not been easily accessible to most researchers. This current study, thus,tried to evaluate the usability of 4CH-Mouse coil (Philips Healthcare, Best, the Netherlands) forpreclinical investigations in clinical 3T MR scan environment. We evaluated the effects of ischemicpreconditioning (IP) in the mouse stroke model with clinical 3T MR scanner and 4CH-Mouse coil. Materials and Methods: Experiments were performed on male C57BL/6 mice that either received the IP or sham operation (control). Three different MR sequences including diffusion weighted images (DWI), T2-weighted images (T2WI), and fluid attenuated inversion recovery (FLAIR) were performed on the mouse brains following 24, 72 hours of middle cerebral artery occlusion (MCAO) and analyzed for infarct lesions. Results: The images showed that the IP-treated mouse brains had significantly smaller infarct volumes compared to the control group. Of the MR sequences employed, the T2WI showed the highest level of correlations with postmortem infarct volume measurements. Conclusions: The clinical 3T MR scanner turned out to have a solid potential as a practical tool for imaging small animal brains. MR sequences including DWI, T2WI, FLAIR were obtained with acceptable resolution and in a reasonable time constraint in evaluating a mouse stroke model brain.

  12. A Simple Methodology for Conversion of Mouse Monoclonal Antibody to Human-Mouse Chimeric Form

    Vinh T. Dang


    Full Text Available Passive immunotherapy has mainly been used as a therapy against cancer and inflammatory conditions. Recent studies have shown that monoclonal antibody-(mAb- based passive immunotherapy is a promising approach to combat virus infection. Specific mouse mAbs can be routinely generated in large amounts with the use of hybridoma technology but these cannot be used for therapy in human beings due to their immunogenicity. Therefore, the development of chimeric and humanized mAbs is important for therapeutic purpose. This is facilitated by a variety of molecular techniques like recombinant DNA technology and the better understanding of the structure and function of antibody. The human-mouse chimeric forms allow detailed analysis of the mechanism of inhibition and the potential for therapeutic applications. Here, a step-by-step description of the conversion process will be described. The commercial availability of the reagents required in each step means that this experimentation can be easily set up in research laboratories.

  13. Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies.

    Shimbo, Miki; Kudo, Takashi; Hamada, Michito; Jeon, Hyojung; Imamura, Yuki; Asano, Keigo; Okada, Risa; Tsunakawa, Yuki; Mizuno, Seiya; Yagami, Ken-Ichi; Ishikawa, Chihiro; Li, Haiyan; Shiga, Takashi; Ishida, Junji; Hamada, Juri; Murata, Kazuya; Ishimaru, Tomohiro; Hashimoto, Misuzu; Fukamizu, Akiyoshi; Yamane, Mutsumi; Ikawa, Masahito; Morita, Hironobu; Shinohara, Masahiro; Asahara, Hiroshi; Akiyama, Taishin; Akiyama, Nobuko; Sasanuma, Hiroki; Yoshida, Nobuaki; Zhou, Rui; Wang, Ying-Ying; Ito, Taito; Kokubu, Yuko; Noguchi, Taka-Aki K; Ishimine, Hisako; Kurisaki, Akira; Shiba, Dai; Mizuno, Hiroyasu; Shirakawa, Masaki; Ito, Naoki; Takeda, Shin; Takahashi, Satoru


    The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module ("Kibo") on the International Space Station. The CBEF provides "space-based controls" by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments. PMID:26822934

  14. Characterization of a pneumococcal meningitis mouse model

    Mook-Kanamori Barry


    Full Text Available Abstract Background S. pneumoniae is the most common causative agent of meningitis, and is associated with high morbidity and mortality. We aimed to develop an integrated and representative pneumococcal meningitis mouse model resembling the human situation. Methods Adult mice (C57BL/6 were inoculated in the cisterna magna with increasing doses of S. pneumoniae serotype 3 colony forming units (CFU; n = 24, 104, 105, 106 and 107 CFU and survival studies were performed. Cerebrospinal fluid (CSF, brain, blood, spleen, and lungs were collected. Subsequently, mice were inoculated with 104 CFU S. pneumoniae serotype 3 and sacrificed at 6 (n = 6 and 30 hours (n = 6. Outcome parameters were bacterial outgrowth, clinical score, and cytokine and chemokine levels (using Luminex® in CSF, blood and brain. Meningeal inflammation, neutrophil infiltration, parenchymal and subarachnoidal hemorrhages, microglial activation and hippocampal apoptosis were assessed in histopathological studies. Results Lower doses of bacteria delayed onset of illness and time of death (median survival CFU 104, 56 hrs; 105, 38 hrs, 106, 28 hrs. 107, 24 hrs. Bacterial titers in brain and CSF were similar in all mice at the end-stage of disease independent of inoculation dose, though bacterial outgrowth in the systemic compartment was less at lower inoculation doses. At 30 hours after inoculation with 104 CFU of S. pneumoniae, blood levels of KC, IL6, MIP-2 and IFN- γ were elevated, as were brain homogenate levels of KC, MIP-2, IL-6, IL-1β and RANTES. Brain histology uniformly showed meningeal inflammation at 6 hours, and, neutrophil infiltration, microglial activation, and hippocampal apoptosis at 30 hours. Parenchymal and subarachnoidal and cortical hemorrhages were seen in 5 of 6 and 3 of 6 mice at 6 and 30 hours, respectively. Conclusion We have developed and validated a murine model of pneumococcal meningitis.

  15. Radioadaptive Cytoprotective Pathways in the Mouse Retina

    Zanello, Susana B.; Wotring, V.; Theriot, C.; Ploutz-Snyder, R.; Zhang, Y.; Wu, H.


    Exposure to cosmic radiation implies a risk of tissue degeneration. Radiation retinopathy is a complication of radiotherapy and exhibits common features with other retinopathies and neuropathies. Exposure to a low radiation dose elicits protective cellular events (radioadaptive response), reducing the stress of a subsequent higher dose. To assess the risk of radiation-induced retinal changes and the extent to which a small priming dose reduces this risk, we used a mouse model exposed to a source of Cs-137-gamma radiation. Gene expression profiling of retinas from non-irradiated control C57BL/6J mice (C) were compared to retinas from mice treated with a low 50 mGy dose (LD), a high 6 Gy dose (HD), and a combined treatment of 50 mGy (priming) and 6 Gy (challenge) doses (LHD). Whole retina RNA was isolated and expression analysis for selected genes performed by RTqPCR. Relevant target genes associated with cell death/survival, oxidative stress, cellular stress response and inflammation pathways, were analyzed. Cellular stress response genes were upregulated at 4 hr after the challenge dose in LHD retinas (Sirt1: 1.5 fold, Hsf1: 1.7 fold, Hspa1a: 2.5 fold; Hif1a: 1.8 fold, Bag1: 1.7). A similar trend was observed in LD animals. Most antioxidant enzymes (Hmox1, Sod2, Prdx1, Cygb, Cat1) and inflammatory mediators (NF B, Ptgs2 and Tgfb1) were upregulated in LHD and LD retinas. Expression of the pro-survival gene Bcl2 was upregulated in LD (6-fold) and LHD (4-fold) retinas. In conclusion, cytoprotective gene networks activation in the retina suggests a radioadaptive response to a priming irradiation dose, with mitigation of the deleterious effects of a subsequent high dose exposure. The enhancement of these cytoprotective mechanisms has potential value as a countermeasure to ocular alterations caused by radiation alone or in combination with other factors in spaceflight environments.

  16. Efferent pathways of the mouse lateral habenula.

    Quina, Lely A; Tempest, Lynne; Ng, Lydia; Harris, Julie A; Ferguson, Susan; Jhou, Thomas C; Turner, Eric E


    The lateral habenula (LHb) is part of the habenula complex of the dorsal thalamus. Recent studies of the LHb have focused on its projections to the ventral tegmental area (VTA) and rostromedial tegmental nucleus (RMTg), which contain γ-aminobutyric acid (GABA)ergic neurons that mediate reward prediction error via inhibition of dopaminergic activity. However, older studies in the rat have also identified LHb outputs to the lateral and posterior hypothalamus, median raphe, dorsal raphe, and dorsal tegmentum. Although these studies have shown that the medial and lateral divisions of the LHb have somewhat distinct projections, the topographic specificity of LHb efferents is not completely understood, and the relative extent of these projections to brainstem targets is unknown. Here we have used anterograde tracing with adeno-associated virus-mediated expression of green fluorescent protein, combined with serial two-photon tomography, to map the efferents of the LHb on a standard coordinate system for the entire mouse brain, and reconstruct the efferent pathways of the LHb in three dimensions. Using automated quantitation of fiber density, we show that in addition to the RMTg, the median raphe, caudal dorsal raphe, and pontine central gray are major recipients of LHb efferents. By using retrograde tract tracing with cholera toxin subunit B, we show that LHb neurons projecting to the hypothalamus, VTA, median raphe, caudal dorsal raphe, and pontine central gray reside in characteristic, but sometimes overlapping regions of the LHb. Together these results provide the anatomical basis for systematic studies of LHb function in neural circuits and behavior in mice. J. Comp. Neurol. 523:32-60, 2015. © 2014 Wiley Periodicals, Inc. PMID:25099741

  17. TRPM3 expression in mouse retina.

    R Lane Brown

    Full Text Available Transient receptor potential (TRP channels constitute a large family of cation permeable ion channels that serve crucial functions in sensory systems by transducing environmental changes into cellular voltage and calcium signals. Within the retina, two closely related members of the melastatin TRP family, TRPM1 and TRPM3, are highly expressed. TRPM1 has been shown to be required for the depolarizing response to light of ON-bipolar cells, but the role of TRPM3 in the retina is unknown. Immunohistochemical staining of mouse retina with an antibody directed against the C-terminus of TRPM3 labeled the inner plexiform layer (IPL and a subset of cells in the ganglion cell layer. Within the IPL, TRPM3 immunofluorescence was markedly stronger in the OFF sublamina than in the ON sublamina. Electroretinogram recordings showed that the scotopic and photopic a- and b-waves of TRPM3(-/- mice are normal indicating that TRPM3 does not play a major role in visual processing in the outer retina. TRPM3 activity was measured by calcium imaging and patch-clamp recording of immunopurified retinal ganglion cells. Application of the TRPM3 agonist, pregnenolone sulfate (PS, stimulated increases in intracellular calcium in ~40% of cells from wild type and TRPM1(‑/‑ mice, and the PS-stimulated increases in calcium were blocked by co-application of mefenamic acid, a TRPM3 antagonist. No PS-stimulated changes in fluorescence were observed in ganglion cells from TRPM3(-/- mice. Similarly, PS-stimulated currents that could be blocked by mefenamic acid were recorded from wild type retinal ganglion cells but were absent in ganglion cells from TRPM3-/- mice.

  18. Ion channels modulating mouse dendritic cell functions.

    Matzner, Nicole; Zemtsova, Irina M; Nguyen, Thi Xuan; Duszenko, Michael; Shumilina, Ekaterina; Lang, Florian


    Ca(2+)-mediated signal transduction pathways play a central regulatory role in dendritic cell (DC) responses to diverse Ags. However, the mechanisms leading to increased [Ca(2+)](i) upon DC activation remained ill-defined. In the present study, LPS treatment (100 ng/ml) of mouse DCs resulted in a rapid increase in [Ca(2+)](i), which was due to Ca(2+) release from intracellular stores and influx of extracellular Ca(2+) across the cell membrane. In whole-cell voltage-clamp experiments, LPS-induced currents exhibited properties similar to the currents through the Ca(2+) release-activated Ca(2+) channels (CRAC). These currents were highly selective for Ca(2+), exhibited a prominent inward rectification of the current-voltage relationship, and showed an anomalous mole fraction and a fast Ca(2+)-dependent inactivation. In addition, the LPS-induced increase of [Ca(2+)](i) was sensitive to margatoxin and ICAGEN-4, both inhibitors of voltage-gated K(+) (Kv) channels Kv1.3 and Kv1.5, respectively. MHC class II expression, CCL21-dependent migration, and TNF-alpha and IL-6 production decreased, whereas phagocytic capacity increased in LPS-stimulated DCs in the presence of both Kv channel inhibitors as well as the I(CRAC) inhibitor SKF-96365. Taken together, our results demonstrate that Ca(2+) influx in LPS-stimulated DCs occurs via Ca(2+) release-activated Ca(2+) channels, is sensitive to Kv channel activity, and is in turn critically important for DC maturation and functions. PMID:18981098

  19. Transgenic mouse offspring generated by ROSI.

    Moreira, Pedro; Pérez-Cerezales, Serafín; Laguna, Ricardo; Fernández-Gonzalez, Raúl; Sanjuanbenito, Belén Pintado; Gutiérrez-Adán, Alfonso


    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

  20. Characterization of a mouse model of headache.

    Huang, Dongyue; Ren, Lynn; Qiu, Chang-Shen; Liu, Ping; Peterson, Jonathan; Yanagawa, Yuchio; Cao, Yu-Qing


    Migraine and other primary headache disorders affect a large population and cause debilitating pain. Establishing animal models that display behavioral correlates of long-lasting and ongoing headache, the most common and disabling symptom of migraine, is vital for the elucidation of disease mechanisms and identification of drug targets. We have developed a mouse model of headache, using dural application of capsaicin along with a mixture of inflammatory mediators (IScap) to simulate the induction of a headache episode. This elicited intermittent head-directed wiping and scratching as well as the phosphorylation of c-Jun N-terminal kinase in trigeminal ganglion neurons. Interestingly, dural application of IScap preferentially induced FOS protein expression in the excitatory but not inhibitory cervical/medullary dorsal horn neurons. The duration of IScap-induced behavior and the number of FOS-positive neurons correlated positively in individual mice; both were reduced to the control level by the pretreatment of antimigraine drug sumatriptan. Dural application of CGRP(8-37), the calcitonin gene-related peptide (CGRP) receptor antagonist, also effectively blocked IScap-induced behavior, which suggests that the release of endogenous CGRP in the dura is necessary for IScap-induced nociception. These data suggest that dural IScap-induced nocifensive behavior in mice may be mechanistically related to the ongoing headache in humans. In addition, dural application of IScap increased resting time in female mice. Taken together, we present the first detailed study using dural application of IScap in mice. This headache model can be applied to genetically modified mice to facilitate research on the mechanisms and therapeutic targets for migraine headache. PMID:27058678

  1. Claudin immunolocalization in neonatal mouse epithelial tissues.

    Troy, Tammy-Claire; Arabzadeh, Azadeh; Yerlikaya, Seda; Turksen, Kursad


    Emerging evidence supports the notion that claudins (Cldns) are dynamically regulated under normal conditions to respond to the selective permeability requirements of various tissues, and that their expression is developmentally controlled. We describe the localization of those Cldns that we have previously demonstrated to be functionally important in epidermal differentiation and the formation of the epidermal permeability barrier, e.g., Cldn1, Cldn6, Cldn11, and Cldn18, and the presence of Cldn3 and Cldn5 in various neonatal mouse epithelia including the epidermis, nail, oral mucosa, tongue, and stomach. Cldn1 is localized in the differentiated and/or undifferentiated compartments of the epidermis and nail and in the dorsal surface of the tongue and glandular compartment of the stomach but is absent from the oral mucosa and the keratinized compartment of the stomach. Cldn3 is present in the basal cells of the nail matrix and both compartments of the murine stomach but not in the epidermis, oral mucosa, or tongue. Cldn5 is found in the glandular compartment of the stomach but not in the epidermis, nail unit, oral mucosa, forestomach, and tongue. Cldn6, Cldn11, and Cldn18 occur in the differentiating suprabasal compartment of the epidermis, nail, and oral mucosa and in the dorsal and ventral surfaces of the tongue and the keratinized squamous epithelium of the stomach. The simple columnar epithelium of the glandular stomach stains for Cldn18 and reveals a non-membranous pattern for Cldn6 and Cldn11 expression. Our results demonstrate differential Cldn protein profiles in various epithelial tissues and their differentiation stages. Although the molecular mechanisms regulating Cldn expression are unknown, elucidation of their differential localization patterns in tissues with diverse permeability requirements should provide a better understanding of the role of tight junctions in tissue function. PMID:17828607

  2. Chromosome anomalies in mouse oocytes after irradiation

    We investigated the cytogenetic effects of X-rays on unfertilized mouse oocytes. NMRI females received an irradiation with 0, 22.2, 66.6, 200, and 600 R during the preovulatory phase 3 hrs after HCG (human chorionic gonadotrophin). This is a stage during oogenesis in which the oocytes pass from late dictyotene to diakinesis. Chromosome anlysis was per formed after ovulation at metaphase II. From these experiments we can draw the following conclusions: X-rays induced during the preovulatory phase a high number of chromosome anomalies. Among these, structural anomalies prevail. 7 out of 144 ovulated oocytes in matched controls carried such an abnormality, whereas after irradiation we observed with 22.2, 66.6, 200, and 600 R, 11 out of 72, 34 out of 108, 89 out of 102, and 122 out of 124, respectively. Irradiation seems also to affect the chromosome segregation during the 1. meiotic division, as we observed after 22.2, 66.6 and 200 R a total of 6 oocytes out of 204 with a supernummary chromosome. In controls, however, no hyperploidy was found in 143 ova. This increase, however, was not significant. Chromosome anomalies, e.g. breaks and deletions that go back to a one-break event increased linearly with increasing dose. Exchanges, however, going back to two-break events fittet best to the linear-quadratic dose-response model. The dose of 600 R seems to represent a kind of borderline in this experiment, because nearly all (122 out 124) carried at least one structural chromosome anomaly. It is also this dose after which the highest frequency of reciprocal translocations was observed in a humpshaped slope in spermatocytes after irradiation of spermatogonia (Preston and Brewen, 1973). With an increasing dosage up to 1,200 R the frequency of translocations decrease again. The elimination of cells, crossing this borderline, might be due to genetic or non-genetic effects. (orig./GSE)

  3. Mass spectrometry analysis of hepcidin peptides in experimental mouse models.

    Harold Tjalsma

    Full Text Available The mouse is a valuable model for unravelling the role of hepcidin in iron homeostasis, however, such studies still report hepcidin mRNA levels as a surrogate marker for bioactive hepcidin in its pivotal function to block ferroportin-mediated iron transport. Here, we aimed to assess bioactive mouse Hepcidin-1 (Hep-1 and its paralogue Hepcidin-2 (Hep-2 at the peptide level. To this purpose, Fourier transform ion cyclotron resonance (FTICR and tandem-MS was used for hepcidin identification, after which a time-of-flight (TOF MS-based methodology was exploited to routinely determine Hep-1 and -2 levels in mouse serum and urine. This method was biologically validated by hepcidin assessment in: i 3 mouse strains (C57Bl/6; DBA/2 and BABL/c upon stimulation with intravenous iron and LPS, ii homozygous Hfe knock out, homozygous transferrin receptor 2 (Y245X mutated mice and double affected mice, and iii mice treated with a sublethal hepatotoxic dose of paracetamol. The results showed that detection of Hep-1 was restricted to serum, whereas Hep-2 and its presumed isoforms were predominantly present in urine. Elevations in serum Hep-1 and urine Hep-2 upon intravenous iron or LPS were only moderate and varied considerably between mouse strains. Serum Hep-1 was decreased in all three hemochromatosis models, being lowest in the double affected mice. Serum Hep-1 levels correlated with liver hepcidin-1 gene expression, while acute liver damage by paracetamol depleted Hep-1 from serum. Furthermore, serum Hep-1 appeared to be an excellent indicator of splenic iron accumulation. In conclusion, Hep-1 and Hep-2 peptide responses in experimental mouse agree with the known biology of hepcidin mRNA regulators, and their measurement can now be implemented in experimental mouse models to provide novel insights in post-transcriptional regulation, hepcidin function, and kinetics.

  4. Mouse transcobalamin has features resembling both human transcobalamin and haptocorrin.

    Katrine Hygum

    Full Text Available In humans, the cobalamin (Cbl -binding protein transcobalamin (TC transports Cbl from the intestine and into all the cells of the body, whereas the glycoprotein haptocorrin (HC, which is present in both blood and exocrine secretions, is able to bind also corrinoids other than Cbl. The aim of this study is to explore the expression of the Cbl-binding protein HC as well as TC in mice. BLAST analysis showed no homologous gene coding for HC in mice. Submaxillary glands and serum displayed one protein capable of binding Cbl. This Cbl-binding protein was purified from 300 submaxillary glands by affinity chromatography. Subsequent sequencing identified the protein as TC. Further characterization in terms of glycosylation status and binding specificity to the Cbl-analogue cobinamide revealed that mouse TC does not bind Concanavalin A sepharose (like human TC, but is capable of binding cobinamide (like human HC. Antibodies raised against mouse TC identified the protein in secretory cells of the submaxillary gland and in the ducts of the mammary gland, i.e. at locations where HC is also found in humans. Analysis of the TC-mRNA level showed a high TC transcript level in these glands and also in the kidney. By precipitation to insolubilised antibodies against mouse TC, we also showed that >97% of the Cbl-binding capacity and >98% of the Cbl were precipitated in serum. This indicates that TC is the only Cbl-binding protein in the mouse circulation. Our data show that TC but not HC is present in the mouse. Mouse TC is observed in tissues where humans express TC and/or HC. Mouse TC has features in common with both human TC and HC. Our results suggest that the Cbl-binding proteins present in the circulation and exocrine glands may vary amongst species.

  5. Operant sensation seeking in the mouse.

    Olsen, Christopher M; Winder, Danny G


    Operant methods are powerful behavioral tools for the study of motivated behavior. These 'self-administration' methods have been used extensively in drug addiction research due to their high construct validity. Operant studies provide researchers a tool for preclinical investigation of several aspects of the addiction process. For example, mechanisms of acute reinforcement (both drug and non-drug) can be tested using pharmacological or genetic tools to determine the ability of a molecular target to influence self-administration behavior. Additionally, drug or food seeking behaviors can be studied in the absence of the primary reinforcer, and the ability of pharmacological compounds to disrupt this process is a preclinical model for discovery of molecular targets and compounds that may be useful for the treatment of addiction. One problem with performing intravenous drug self-administration studies in the mouse is the technical difficulty of maintaining catheter patency. Attrition rates in these experiments are high and can reach 40% or higher. Another general problem with drug self-administration is discerning which pharmacologically-induced effects of the reinforcer produce specific behaviors. For example, measurement of the reinforcing and neurological effects of psychostimulants can be confounded by their psychomotor effects. Operant methods using food reinforcement can avoid these pitfalls, although their utility in studying drug addiction is limited by the fact that some manipulations that alter drug self-administration have a minimal impact on food self-administration. For example, mesolimbic dopamine lesion or knockout of the D1 dopamine receptor reduce cocaine self-administration without having a significant impact on food self-administration. Sensory stimuli have been described for their ability to support operant responding as primary reinforcers (i.e. not conditioned reinforcers). Auditory and visual stimuli are self-administered by several species

  6. Assisting People with Multiple Disabilities Improve Their Computer-Pointing Efficiency with Hand Swing through a Standard Mouse

    Shih, Ching-Hsiang; Chiu, Sheng-Kai; Chu, Chiung-Ling; Shih, Ching-Tien; Liao, Yung-Kun; Lin, Chia-Chen


    This study evaluated whether two people with multiple disabilities would be able to improve their pointing performance using hand swing with a standard mouse through an Extended Dynamic Pointing Assistive Program (EDPAP) and a newly developed mouse driver (i.e., a new mouse driver replaces standard mouse driver, and changes a mouse into a precise…

  7. Assisting People with Multiple Disabilities and Minimal Motor Behavior to Control Environmental Stimulation through a Mouse Wheel

    Shih, Ching-Hsiang; Shih, Ching-Tien; Lin, Kun-Tsan; Chiang, Ming-Shan


    This study assessed whether two people with profound multiple disabilities and minimal motor behavior would be able to control environmental stimulation using thumb poke ability with a mouse wheel and a newly developed mouse driver (i.e., a new mouse driver replacing standard mouse driver, and turning a mouse into a precise thumb poke detector).…

  8. The endothelial cyclooxygenase pathway: Insights from mouse arteries.

    Luo, Wenhong; Liu, Bin; Zhou, Yingbi


    To date, cyclooxygenase-2 (COX-2) is commonly believed to be the major mediator of endothelial prostacyclin (prostaglandin I2; PGI2) synthesis that balances the effect of thromboxane (Tx) A2 synthesis mediated by the other COX isoform, COX-1 in platelets. Accordingly, selective inhibition of COX-2 is considered to cause vasoconstriction, platelet aggregation, and hence increase the incidence of cardiovascular events. This idea has been claimed to be substantiated by experiments on mouse models, some of which are deficient in one of the two COX isoforms. However, results from our studies and those of others using similar mouse models suggest that COX-1 is the major functional isoform in vascular endothelium. Also, although PGI2 is recognized as a potent vasodilator, in some arteries endothelial COX activation causes vasoconstrictor response. This has again been recognized by studies, especially those performed on mouse arteries, to result largely from endothelial PGI2 synthesis. Therefore, evidence that supports a role for COX-1 as the major mediator of PGI2 synthesis in mouse vascular endothelium, reasons for the inconsistency, and results that elucidate underlying mechanisms for divergent vasomotor reactions to endothelial COX activation will be discussed in this review. In addition, we address the possible pathological implications and limitations of findings obtained from studies performed on mouse arteries. PMID:27020548

  9. Barrier qualities of the mouse eye to topically applied drugs.

    Wang, Zhao; Do, Chi Wai; Avila, Marcel Y; Stone, Richard A; Jacobson, Kenneth A; Civan, Mortimer M


    The mouse eye displays unusually rapid intraocular pressure (IOP) responses to topically applied drugs as measured by the invasive servo-null micropipette system (SNMS). To learn if the time course reflected rapid drug transfer across the thin mouse cornea and sclera, we monitored a different parameter, pupillary size, following topical application of droplets containing 40 microM (0.073 microg) carbachol. No miosis developed from this low carbachol concentration unless the cornea was impaled with an exploring micropipette as used in the SNMS. We also compared the mouse IOP response to several purinergic drugs, measured by the invasive SNMS and non-invasive pneumotonometry. Responses to the previously studied non-selective adenosine-receptor (AR) agonist adenosine, the A(3)-selective agonist Cl-IB-MECA and the A(3)-selective antagonist MRS 1191 were all enhanced to varying degrees, in time and magnitude, by corneal impalement. We conclude that the thin ocular coats of the mouse eye actually present a substantial barrier to drug penetration. Corneal impalement with even fine-tipped micropipettes can significantly enhance entry of topically-applied drugs into the mouse aqueous humor, reflecting either direct diffusion around the tip or a more complex impalement-triggered change in ocular barrier properties. Comparison of invasive and non-invasive measurement methods can document drug efficacy at intraocular target sites even if topical drug penetration is too slow to manifest convincing physiologic effects in intact eyes. PMID:17490649

  10. A Network of Splice Isoforms for the Mouse.

    Li, Hong-Dong; Menon, Rajasree; Eksi, Ridvan; Guerler, Aysam; Zhang, Yang; Omenn, Gilbert S; Guan, Yuanfang


    The laboratory mouse is the primary mammalian species used for studying alternative splicing events. Recent studies have generated computational models to predict functions for splice isoforms in the mouse. However, the functional relationship network, describing the probability of splice isoforms participating in the same biological process or pathway, has not yet been studied in the mouse. Here we describe a rich genome-wide resource of mouse networks at the isoform level, which was generated using a unique framework that was originally developed to infer isoform functions. This network was built through integrating heterogeneous genomic and protein data, including RNA-seq, exon array, protein docking and pseudo-amino acid composition. Through simulation and cross-validation studies, we demonstrated the accuracy of the algorithm in predicting isoform-level functional relationships. We showed that this network enables the users to reveal functional differences of the isoforms of the same gene, as illustrated by literature evidence with Anxa6 (annexin a6) as an example. We expect this work will become a useful resource for the mouse genetics community to understand gene functions. The network is publicly available at: PMID:27079421