CORE B: Animal Model Core

动物模型中心（AMC）的职责是为各个项目提供专家 协助动物模型实验。AMC将对管理层进行监督， 治疗转基因和野生型小鼠用于肿瘤发生研究。它将提供并保持当前的 动物相关数据的中央存储库。它将负责肿瘤检测和监测， 尸检、组织采集和分发给项目研究人员。AMC将监督 将组织运送给我们的顾问/合作者和外部顾问委员会成员Robert卡迪夫博士， 加州大学戴维斯比较医学中心。AMC将提供统一的组织样本， 提取物提供给研究人员进行生化和分子研究。这些功能将确保 三个组成项目中使用的动物组织的一致性，并允许直接比较 对相同组织的各种研究的结果。这些程序促进有效利用 组织和动物，减少所需的动物总数。 Drs. Sonenshein，Seldin和Sherr在过去的10年里密切合作， 设计并实施了实验，并发现这种策略是高产和高效的。博士 塞尔丁在生产转基因小鼠方面有着丰富的经验，他是这项设计的一个资源 并执行所有小鼠研究。在上一个赠款期间，Adrianne Rogers博士是 核心她的努力集中在老鼠模型上，她的领导能力是无价的。然而，老鼠的研究 不属于更新申请的一部分，罗杰斯博士（本月即将退休）将担任 非正式顾问和合作者，但不是核心共同领导人。 具体成就 集中的动物核心已经完成了多项常见的任务，如果携带这些任务将是浪费的 三个项目，而不是核心。这些任务对这三个国家都至关重要， 项目包括：1）开发DMBA治疗小鼠乳腺肿瘤形成的条件，2） 用DMBA处理小鼠并制备用于组织学和分子生物学的小鼠组织样品 分析，3）小鼠尸检，提取乳腺组织RNA和蛋白质并将其分布 4）在实验前和实验过程中， 致癌作用研究，5）协助开发和培育5个转基因小鼠系[MMTVc-1]。 rel（Romieu-Mourez等人，2003）、MMTV-SR-kB-a（Demicco等人，2005年），MMTV-c-rel x MMTV-CK2 双transgenics（Eddy等人，2005）、LEF-GFP和MMTV-AhR）]，6）尾DMA的集中制备 和所有转基因系的基因分型，7）提供处于定时妊娠阶段的小鼠用于研究，8） 建立和维护关于小鼠治疗、健康和尸检的可访问数据库， 分子结果，9）进行动物MRI以监测肿瘤生长和转移。这些任务 由该计划雇用的动物和实验室助理进行。它们需要 将继续有效地提供相当高水平的专门知识、监督和培训， Seldin、Xiao和Yang博士的项目。在联合国主持下的这些资源的重复 单个RO 1需要更多的动物，更多的技术支持， 技术和协议的一致性的优势，使可靠的比较研究。 因此，在财务和后勤方面，资产管理公司对该计划有相当大的附加值 项目

The responsibility of the Animal Model Core (AMC) is to provide the individual projects with expert assistance with animal model experimentation. The AMC will provide oversight of the management and treatment of transgenic and wildtype mice for tumorigenesis studies. It will provide and keep current a central repository of data related to the animals. It will be responsible for tumor detection and monitoring, necropsy, and tissue collection and distribution to the Program investigators. The AMC will oversee shipping tissues to our consultant/collaborator and External Advisory Board member Dr. Robert Cardiff of the U.C. Davis Center for Comparative Medicine. The AMC will provide uniform tissue samples and extracts to investigators for their biochemical and molecular studies. These functions will assure consistency of the animal tissues used in the three component projects and permit direct comparisons of the results of a wide variety of studies on the same tissues. These procedures promote efficient use of tissues and animals, reducing the overall numbers of animals needed. Drs. Sonenshein, Seldin, and Sherr have worked closely over the past 10 years on collaboratively designed and implemented experiments and found this strategy to be highly productive and efficient. Dr. Seldin, with his considerable experience producing transgenic mice, has been a resource in the design and execution of all mouse studies. In the previous grant period, Dr. Adrianne Rogers was Leader of the Core. Her efforts focused upon the rat models, and her leadership was invaluable. However, rat studies are not part of the renewal application, and Dr. Rogers (who is retiring this month) will serve as an informal consultant and collaborator but not as Core co-Leader. Specific Accomplishments The centralized animal core has performed multiple common tasks that would be wasteful if carried out by the three individual projects instead of the Core. These tasks, which are crucial to all three projects, include: 1) developing DMBA treatment conditions for mouse mammary tumor formation, 2) treatment of mice with DMBA and preparing mouse tissue samples for histologic and molecular analyses, 3) necropsy of mice and extraction of mammary tissue RNA and protein and distributing them to the laboratories of the project leaders, 4) caring for and monitoring mice before and during carcinogenesis studies, 5) assisting with development and breeding of 5 transgenic mouse lines [MMTVc- rel (Romieu-Mourez et al., 2003), MMTV-SR-kB-a (Demicco et al., 2005), MMTV-c-rel x MMTV-CK2 bitransgenics (Eddy et al., 2005), LEF-GFP, and MMTV-AhR)], 6) centralizing preparation of tail DMA and genotyping for all transgenic lines, 7) providing mice at timed stages of pregnancy for study, 8) establishing and maintaining an accessible database on mouse treatment, health, and necropsy and molecular results, 9) performing animal MRI to monitor tumor growth and metastases. These tasks are being carried out by animal and laboratory assistants employed by the program. They require a considerable level of expertise, supervision and training, which will continue to be effectively provided in the Program Project by Drs. Seldin, Xiao, and Yang. Duplication of these resources under the auspices of individual RO1s would have required many more animals, more technical support, and would not have the advantage of uniformity of techniques and protocols that has allowed reliable comparative studies. Thus, on financial and logistical grounds there is considerable value added of the AMC to the Program Project.