DESCRIPTION: State the application's broad, long-term objectives and specific aims, making reference to the health relatedness of the project. Describe concisely the research design and methods for achieving these goals. Avoid summaries of past accomplishments and the use of the first person. This abstract is meant to serve as a succinct and accurate description of the proposed work when separated from the application. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. DO NOT EXCEED THE SPACE PROVIDED. This is a resubmission of the first competitive continuing application requesting NIH/NCRR support for the next 5 years of the UC Davis Mutant Mouse Regional Resource Center (UCD-MMRRC). The overall objective of the UCD-MMRRC is to serve as a component of the MMRRC National Program, to accept, maintain, and distribute mutant mouse strains for use in biomedical research. The MMRRC program accepts transgenics, knockouts, and all other kinds of mutant mouse lines at no cost to the donor, and after SPF-rederivation and cryopreservation, distributes breeding stock orgermplasm of genetically, and in many cases phenotypically verified mice for a small fee to requesting investigators for non-commercial, academic research purposes only. The UCD-MMRRC currently has a census of >9000 mutant strains maintained as either actively breeding mousecolonies, frozen embryos or germplasm, and/or embryonic stem cell clones. Further, the UCD-MMRRC serves in a coordinated network with 3 other regional MMRRCs as a center of excellence engaged in research and teaching on the biology of the laboratory mouse, providing the scientific community with professional expertise in mutant mouse biology, colony management, conventional and advanced genotyping and phenotyping capabilities, clinical and anatomic pathology services, strain rescue, infectious disease diagnostics and health care, and other areas. In keeping with this mission, this application states 4 interconnected Specific Aims that focus on continuing maintenance of mutant mouse lines in the resource, acceptance of new lines into the resource, research and development projects that eventually will be transferred to the resource to improve its functional efficiency and capabilities, and finally to provide opportunities for outreach and education and training in mouse biology. These Specific Aims are facilitated by closely linked faculty expertise of the UCD Center for Comparative Medicine (CCM), the UCD Mouse Biology Program (UCD-MBP), and the Schools of Medicine and Veterinary Medicine. These relationships allow leveraging of MMRRCsupport, resulting in expanded opportunities for, and benefit to, the MMRRC National Program and the biomedical and behavioral scientific research community. PERFORMANCE SITE(S) (organization, city, state) University of California, Davis, California KEY PERSONNEL See instructions. Usecontinuation pages as needed to provide the required information in the format shown below. Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name Organization Role on Project Stephen W. Barthold University of California, Davis Principal Investigator K.C. Kent Lloyd University of California, Davis Co-Investigator Robert D. Cardiff University of California, Davis Co-Investigator Stephen M. Griffey University of California, Davis Co-Investigator Jose J. Galvez University of California, Davis Co-Investigator Mari Golub University of California, Davis Co-Investigator Paul A. Luciw University of California, Davis Co-Investigator Alexander D. Borowsky University of California, Davis Co-Investigator Jeffrey P. Gregg University of California, Davis Consultant Simon P. Cherry University of California, Davis Consultant Andrew Fell University of California, Davis Consultant Disclosure Permission Statement Applicable to SBIR/STTR Only. Seeinstructions. CHYes l~1 No PHS 398 (Rev. 05/01) Page 2 Number pages consecutively atthebottom throughout Form Page 2 the application. Do not use suffixes such as 2a, 2b. Principal Investigator/Program Director (Last, First, Middle): Barthold, Stephen W. The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT