Animal Models Core

动物模型核心（AMC）将通过提供必要的转基因小鼠和在小鼠体内生产低传代人类胃肠道癌外植体来支持该计划中的所有研究项目。AMC的使命之一将是维持小鼠进行长期研究，以评估癌症易感性。AMC的第二个使命将是维持转基因菌株的库存（例如，elf、elf/Smad 4、Smad 4、Smad 3、Cdk 4-R24 C突变体、cdk 4无效突变体、htert敲除），并将这些菌株一起繁殖以产生双突变体和三突变体纯合基因型的胎儿。与组织芯B一起工作，这些胎儿将被项目用作胚胎成纤维细胞和肿瘤细胞的来源。具有所需的双重或三重突变基因型的幼崽将构成子代的大部分。为了提供持续的供应以支持研究项目，将需要大量的育种，加上基因型分析以确定合适的个体。AMC的第三个使命是在临床医生和抗癌药物治疗测试项目之间提供协同作用。这种协同作用将以产生和提供具有倾向于产生肿瘤的遗传背景的小鼠或用人肿瘤组织异种移植用于繁殖低传代肿瘤的裸鼠的饲养的形式。所有小鼠将在屏障条件下生产和饲养，以确保持续的无特定病原体状态。在AMC下集中生产和护理这些小鼠将限制处理动物的人员数量，从而进一步保护其健康。此外，通过集中生产和分配这些具有遗传价值的动物，动物核心将能够协调不同项目之间的使用，避免浪费，并实现规模经济，使这些研究能够以比单独进行更少的费用完成。AMC的最后一项使命是充当所有项目和核心的协同枢纽。

The Animal Models Core (AMC) will support all of the research projects in the program by providing the necessary genetically modified mice and producing low-passage in vivo human gastro-intestinal cancer explants in mice. One mission of the AMC will be to maintain mice for long-term studies to evaluate predisposition to cancer. A second mission of the AMC will be maintaining stocks of the genetically modified strains (e.g., elf, elf/Smad4, Smad4, Smad3, Cdk4-R24C mutant, cdk4 null mutant, htert knockout), and to breed these strains together to produce fetuses of double and triple mutant homozygous genotypes. Working with the Tissue Core B, these fetuses will be used as a source of embryonic fibroblasts and tumor cells by the projects. Pups with the desired double or triple mutant genotypes will constitute a large fraction of the progeny. 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 the AMC will be to provide synergy between the clinicians and projects testing anti-cancer drug therapies. This synergy will be in the form of producing, and providing husbandry of mice harboring genetic backgrounds predisposed to making tumors or nude mice xenografted with human tumor tissues for propagating low passage tumors. All mice will be produced and housed under barrier conditions that ensure continuing specific pathogen free status, Centralization of the production and care of these mice under the AMC will limit the number of individuals handling the animals, thereby further safeguarding their health. Moreover, by centralizing the production and dispensation of these genetically valuable animals, the animal core will be able to coordinate usage among the different projects, avoid wastage, and achieve an economy of scale that will permit these studies to be completed at less expense than if undertaken separately. A final mission of the AMC will be to serve as a synergistic hub for all projects and cores.