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胃肠道癌外植体来支持该计划中的所有研究项目。AMC的任务之一将是维持小鼠进行长期研究，以评估患癌症的易感性。AMC的第二个任务将是保持转基因菌株(例如，ELF、ELF/Smad4、Smad4、SMAD3、CDK4-R24C突变、CDK4零突变、hTERT敲除)的库存，并将这些菌株一起繁殖，以产生双重和三重突变纯合子基因的胎儿。与组织核心B合作，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的幼崽将构成后代的一大部分。为了为研究项目提供源源不断的支持，需要进行大量的育种工作，并进行基因分析以确定合适的个体。AMC的第三个使命将是在临床医生和测试抗癌药物疗法的项目之间提供协同作用。这种协同作用的形式将是生产和饲养具有易产生肿瘤的遗传背景的小鼠，或将人肿瘤组织移植到裸鼠身上以繁殖低传代肿瘤。所有小鼠将在屏障条件下生产和饲养，以确保持续的特定病原体无状态，将这些小鼠的生产和护理集中在AMC之下，将限制处理动物的个人数量，从而进一步保护它们的健康。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的更少的费用完成。AMC的最终使命将是作为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.