The Animal Models Core (AMC) will support all of the research projects in the program by providing thenecessary genetically modified mice and producing low-passage in vivo human gastro-intestinal cancerexplants in mice. One mission of the AMC will be to maintain mice for long-term studies to evaluatepredisposition to cancer. A second mission of the AMC will be maintaining stocks of the genetically modifiedstrains (e.g., elf, eif/Smad4, Smad4, Smad3, Cdk4-R24C mutant, cdk4 null mutant, htert knockout), and tobreed these strains together to produce fetuses of double and triple mutant homozygous genotypes. Workingwith the Tissue Core B, these fetuses will be used as a source of embryonic fibroblasts and tumor cells bythe projects. Pups with the desired double or triple mutant genotypes will constitute a large fraction of theprogeny. To provide a continuous supply in support of the research projects a large amount of breeding,coupled with genotype analysis to identify the appropriate individuals will be required. A third mission of theAMC will be to provide synergy between the clinicians and projects testing anti-cancer drug therapies. Thissynergy will be in the form of producing, and providing husbandry of mice harboring genetic backgroundspredisposed to making tumors or nude mice xenografted with human tumor tissues for propagating lowpassagetumors. All mice will be produced and housed under barrier conditions that ensure continuingspecific pathogen free status, Centralization of the production and care of these mice under the AMC willlimit the number of individuals handling the animals, thereby further safeguarding their health. Moreover, bycentralizing the production and dispensation of these genetically valuable animals, the animal core will beable to coordinate usage among the different projects, avoid wastage, and achieve an economy of scale thatwill permit these studies to be completed at less expense than if undertaken separately. A final mission ofthe AMC will be to serve as a synergistic hub for all projects and cores.
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