application) The Genetic Animal Core represents one of the centerpieces of the CSIBD's research program for the next proposed funding period. The availability of powerful murine models of IBD offers the opportunity to assess key aspects of the hypotheses underlying the development of the research program of the CSIBD. In addition, these models will allow defining mechanisms contributing to the expression of chronic intestinal inflammation. Overall, the availability of these murine models allows for a rapid analysis of the contributions of genetic mutations or novel therapeutic agents to the pathogenesis of colitis. Moreover, this Core has the ability to compare and crosscheck the influence of mutations or of therapeutic agents that may illuminate underlying mechanisms in the onset of disease. The genetic mouse models used in this Core are subdivided into three categories: 1) spontaneous chronic colitis; 2) colitis induced by adoptive transfer of wt or mutant T cells into immunodeficient mice; and 3) colitis induced by bone marrow transplantation into immunodeficient mice. In addition, the Core's mandate has been expanded over the past two years in response to the needs of CSIBD investigators to include two additional services: 4) chemically-induced colitis in mutant mice (DSS or TNBS); and 5) isolation of intestinal epithelial lymphocytes and lamina propria lymphocytes from wt and mutant mice. Thus, the overall goals of this Core include provision of these genetic murine models to CSIBD investigators and continued development and refinement of the models themselves. The core currently has a large """"""""menu"""""""" of mice available to center investigators, which is listed in Tables 10 and 11 in the grant application. The core will also, in collaboration with the morphology core, characterize the genetic profile of the experimental animals and parallel documentation of IBD, primarily using PCR and histology. The core will also facilitate obtaining samples from animals and finally will play a role in developing new genetic models.
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