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.
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