CORE B: Animal Model Core

动物模型核心(AMC)的职责是为单个项目提供专家 协助动物模型实验。AMC将提供对管理和 用于肿瘤发生研究的转基因和野生型小鼠的治疗。它将提供并保持最新的 与动物相关的数据的中央存储库。它将负责肿瘤检测和监测， 身体解剖，以及组织收集和分发给项目调查人员。AMC将监督 将纸巾运送给我们的顾问/合作者和外部顾问委员会成员罗伯特·卡迪夫博士 加州大学戴维斯分校比较医学中心。AMC将提供统一的组织样本和 萃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 三个组成部分项目中使用的动物组织的一致性，并允许直接比较 对相同组织进行的各种研究的结果。这些程序促进了对 组织和动物，减少所需动物的总数量。 Sonenshein、Seldin和Sherr博士在过去的10年里密切合作 设计并实施了实验，发现这一策略是高效的。Dr。 塞尔丁拥有制造转基因小鼠的丰富经验，一直是设计中的一个资源。 并进行所有的小鼠研究。在之前的赠款期间，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，对老鼠的研究 不是续签申请的一部分，罗杰斯博士(本月退休)将担任 非正式顾问和合作者，但不是作为核心联合领导者。 具体成就 集中的动物核心执行了多个常见的任务，如果携带这些任务将是浪费的 由三个单独的项目而不是核心。这些任务对这三项任务都是至关重要的 项目，包括：1)开发DMBA治疗小鼠乳腺肿瘤的条件；2) DMBA处理小鼠及制备小鼠组织学和分子生物学标本 分析，3)小鼠尸检及乳腺组织RNA和蛋白质的提取及分布 送到项目负责人的实验室，4)在事前和事中照顾和监测老鼠 致癌研究，5)协助开发和培育5个转基因小鼠系[MMTVc- Rel(Romieu-Mourez等人，2003年)、MMTV-SR-kB-a(Demicco等人，2005年)、MMTV-c-Rel x MMTV-CK2 Bitransgenics(Eddy等人，2005)，Lef-GFP和MMTV-AhR)]，6)尾部DMA的集中制备 和所有转基因品系的基因分型，7)在怀孕的定时阶段提供小鼠用于研究，8) 建立和维护关于老鼠治疗、健康和尸检的可访问数据库，并 分子结果，9)进行动物核磁共振以监测肿瘤的生长和转移。这些任务是 由该计划雇用的动物和实验室助理执行。它们需要一个 相当水平的专门知识、监督和培训，将继续有效地提供 塞尔丁、肖和杨博士的计划项目。这些资源在赞助下的重复使用 个体RO1将需要更多的动物，更多的技术支持，而不是 技术和方案一致的优势使可靠的比较研究成为可能。 因此，在财务和后勤方面，AMC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.