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  • 18th International Mouse Genome Conference (2004)
    Z Bigby T Nizet V Beutler B 1 TSRI La Jolla United States 2 UCSD San Diego United States Surface epithelia constitute the first line of defense against pathogens This defense may depend both upon barrier function and upon specific microbicidal effector molecules In the course of our germline mutagenesis effort we isolated flake flk an ENU induced recessive mutation of C57BL 6 mice which causes progressive alopecia and chronic exfoliative dermatitis These features appeared at weaning age and were more pronounced in older animals Visible disruption of epidermal integrity and spontaneous skin infections requiring antibiotic therapy prompted us to examine the integrity of innate immune function in these mice We utilized luminescence tagged bacterial strains to monitor the progression of dermal infections in vivo and we showed that the flk mutation impairs the clearance of subcutaneous infections by Streptococcus pyogenes and Stapylococcus aureus Gram positive pathogens that elicit innate immune responses by activating Toll like receptor 2 TLR2 Positional cloning sequencing and genetic complementation analysis revealed that flk is a novel allele of the steroyl CoA desaturase 1 gene Scd1 Flake homozygotes are unable to synthesize the monounsaturated fatty acids MUFA palmitoleate C16 1 and oleate C18 1 both

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file48.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    Munich Germany 2 Junior Research Group Infection Genetics German Research Centre for Biotechnology GBF Braunschweig Germany 3 Institute of Molecular Immunology GSF National Research Center for Environment and Health Munich Germany 4 German Mouse Clinic Institute of Experimental Genetics GSF National Research Center for Environment and Health Neuherberg Germany Infectious diseases are a major cause of morbidity and mortality worldwide It is well established that the sex of a host can significantly affect susceptibility to infection A number of reports have shown that patients of one sex are more likely to get an infectious disease and gender is often referred to as risk factor for the severity and outcome of an illness The underlying molecular mechanisms of this predisposition are largely unknown Listeria monocytogenes L m is an intracellular Gram positive bacterium that causes diseases in immunocompromised individuals and pregnant women often with deleterious consequences for the fetus It is also one of the most widely used pathogens in experimental mouse studies that provided the basis for establishing major paradigms in contemporary immunology Although most mouse infection models demonstrate higher resistance in females we made the unexpected observation that female mice are significantly more susceptible to L m infection compared

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file49.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    THE RED CELL AND A TOTALLY SYNERGISTIC NON ERYTHROCYTIC PATHWAY Lin E Marshall V Burt RA Foote SJ The Walter Eliza Hall Institute Parkville Australia P chabaudi infection in mice is a model for the severe anaemia seen in falciparum infections Inbred mice strains are differentially susceptible to malaria We have mapped three loci involved in outcome to this infection and have generated mice reciprocally congenic for these loci on several strains of mouse These congenic animals have phenotypes different from their wildtype parents Parasitaemias are more informative than clinical outcome in differentiating between the congenic animals In one case a congenic animal carrying a locus predicted to encode susceptibility was much more resistant than even the resistant animal Analysis of the ability of red cells from congenic mice to sustain the growth of the parasite has been compared to wildtype using a novel comparative in vivo parasite survival assay Mice congenic for the lmr2 locus demonstrate a curious effect where the origin of the animal receiving the red cells modulates the effect of the red cells This means that a red cell factor interacts with another non red cell factor in a completely synergistic fashion Other haematological parameters also

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file50.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    1 Mahabir E 2 Schmidt J 2 Hrabé de Angelis M 1 1 Institute of Experimental Genetics GSF National Research Center for Environmental and Health Neuherberg Germany 2 Department of Comparative Medicine GSF National Research Center for Environmental and Health Neuherberg Germany Cryobanking of mouse mutants and allocation of specific pathogen free SPF animals is of particular importance for the scientific community Routinely used rederivation methods have to be enhanced by new assisted reproductive technologies e g Zona dissection ICSI but these methods need to be investigated with regard to possible pathogen transmission The most common viral pathogen in mouse facilities the Mouse Hepatitis Virus MHV was chosen to ensure a well defined washing procedure used for in vitro fertilization IVF and to estimate the risk increase by zona microdissection with PALM microbeam laser Zona pellucida ZP intact and laser dissected oocytes used for the IVF were scheduled in three experiment groups oocytes in IVF were exposed to virus during fertilization and culture without washing procedure oocytes in IVF were exposed to virus during fertilization and culture with washing procedure laser microdissected oocytes in IVF were exposed to virus during fertilization and culture with washing procedure Resulting embryos were transferred

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file51.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    Leonardson A 1 Wang S 2 Doss S 2 Yang X 2 Ghazalpour A 2 Davis R 2 Zhang B 2 Horvath S 2 Drake T 2 Lusis A 2 1 Rosetta Inpharmatics LLC Seattle WA United States 2 UCLA School of Medicine Los Angeles CA United States We are utilizing genetic variation between strains of mice to identify genes and pathways contributing to atherosclerosis and diabetes Using QTL mapping numerous relevant loci have been identified and some positional candidates have been confirmed We are now developing approaches that integrate traditional gene mapping and expression array data to help identify genes and elucidate pathways involved in these complex diseases Thus far we have applied expression based mapping strategies to genetic crosses between strains DBA and C57BL 6 liver and strains C3H and C57BL 6 liver fat muscle brain Each cross has resulted in the identification of thousands of expression QTL eQTL About a third of these appear to result from cis acting variations that is the eQTL maps over the gene encoding the transcript in question These have been validated using a classical cis trans test with F1 mice in which the levels of transcript from each allele were determined

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file13.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    2 MRC Mammalian Genetics Unit Harwell Didcot United Kingdom 3 Department of Human Anatomy and Genetics Oxford University Oxford United Kingdom 4 Department of Biochemistry New York University Medical Center New York United States 5 Swansea Clinical School University of Wales Swansea Singleton Park Swansea United Kingdom 6 Department of Pharmacology The School of Pharmacy London United Kingdom The identification of the genes and molecular pathways that are associated with human neurobehavioral disorders has been difficult because they are heterogeneous complex and likely involve multiple genetic loci Mouse models that are based on intermediate signatures of psychiatric disease hold promise as an approach to dissecting the molecular basis of these disorders N ethyl N nitrosourea ENU mutagenesis in the mouse when coupled to a battery of sensitive behavioural screens is an effective way of creating and identifying novel mouse behavioral mutants We screened 9 000 F1 mice in a dominant ENU screen for locomotor activity We report on the identification of Jenna a hyperactive mouse mutant with an enhanced acoustic startle response Histological analysis revealed that the Jenna mouse line also has an enlarged superior colliculus a region of the brain implicated in regulating the startle response We undertook positional

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file52.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    DS Nadeau JH Case Western Reserve University Cleveland United States Metabolic syndrome MetS refers to a constellation of cardiovascular risk factors that include obesity hypertension dyslipidemia and altered glucose homeostasis leading to diabetes Male C57BL 6J mice fed a high fat high sucrose HF HS diet are a model of MetS To evaluate the contribution of genetic background diet and gender on the MetS phenotype in this model 21 MetS related traits were examined in male and female A J and C57BL 6J At 5 weeks of age 30 mice per group were fed either the HF HS or maintenance diet for 16 weeks After 15 weeks a fasted IPGTT was performed At 16 weeks body weight length measures blood and liver were collected following a fast Plasma ALT AST cholesterol glucose insulin NEFA and triglycerides as well as liver weight and triglyceride content were measured Data were analyzed using a factorial ANOVA design with planned comparison tests per trait and an experiment wide modified Bonferroni correction was applied Fourteen traits showed significant background effects 17 significant diet effects and 16 significant gender effects Interactions between factors were also noted for 13 traits Comparing A J and C57BL 6J on

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file53.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    R 2 Townsend S 1 Brown S 1 1 MRC Harwell United Kingdom 2 Tokyo Metropolitan Institute of Medical Science Rinshoken Tokyo Japan Stereocilia on the surface of hair cells are vital for the process of auditory transduction Stereocilia develop in bundles with a regular staircase pattern whose actin core is organised such that the barbed ends of actin filaments are located at the stereocilia tips where there is a continuous cycle of renewal of actin filaments by addition of actin monomers What little we know of the molecular processes that control actin polymerisation and stereocilia growth come from studies of mouse mutants with defects in stereocilia development including the shaker2 myosin XVa and whirler mutants The PDZ protein whirlin is known by virtue of the whirler mutation to be involved in the process of stereocilia organisation Mburu et al Nature Genetics 2003 We have investigated the expression of whirlin and myosin XVa in developing stereocilia in wild type and whirler and shaker2 mutants Whirlin localises to the actin free zone at the tips of stereocilia Expression of whirlin is dynamic during stereocilia growth demonstrating an ordered appearance and fade out across the stereocilia rows and revealing a novel molecular

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file54.shtml (2016-02-17)
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