Resource Section This proposal seeks renewal of 5 year support for the infrastructure, personnel, and resources of the Mutant Mouse Resource and Research Center (MMRRC) at the University of California (UC) Davis (MMRRC-UCD). Since its inception 20 years ago, the MMRRC-UCD has been one of the primary mutant mouse archive and distribution repositories in the world. As the largest of the 4 Centers in the MMRRC Consortium, the MMRRC- UCD has assumed a position of leadership in innovation and resource development. The MMRRC-UCD has introduced new products (e.g., KOMP knockout first alleles in ES cells, CRISPR/Cas9 genome edited alleles in zygotes) and initiated new services (e.g., blastocyst injection, ICSI, speed congenics, genetic variant modeling, microbiome analysis) that have added scientific value to mouse models submitted to the MMRRC, which in turn has enhanced utilization of the MMRRC by the scientific research community. As a result, to date the MMRRC-UCD leads the Consortium in the number of alleles archived (50,040 out of 59,847), orders (6,293 out of 13,165), and investigators served (4,372 out of 6477) at 2,445 institutions in 23 countries. The MMRRC- UCD has leveraged its infrastructure and expertise to extend its service role by contracting with categorical NIH institutes (e.g., NHLBI BayGenomics project), biotechnology companies (Genentech), and several organizations (e.g., the BaSH Consortium) to archive, distribute, custom breed, genotype, and phenotype 1000?s of transgenic and knockout, gene-targeted ES cell lines, BAC-transgenic, CRE, ENU-induced, and other mutant mouse collections. In addition, the MMRRC-UCD has worked with its MMRRC Consortium partners and NIH program staff to develop and implement advertising and marketing strategies, database management and informatics applications, website and online resources, customer and user services, operating procedures and protocols, and policies and practicies for shared governance. Further, over the last several years, the MMRRC-UCD completed several research projects in multiple areas that have enhanced operations of the resource, including in cryopreservation, gut microbiome analysis, mouse analgesics administration, genetic variant modeling using CRISPR/Cas9, and more. Over the next 5 years, the MMRRC- UCD looks forward to the assignment of another ~250 mouse lines (Type 1), providing users access to several new services including Fast-Track Genome Editing and Genomic Integration Analysis, and conducting 3 new research projects in the areas of microbiome transplantation, quantitative embryo evaluation, and multi-omic molecular analyses. By archiving and delivering research mouse products and services effectively and efficiently, and by conducting applied research activities to improve operations of the resource, the MMRRC- UCD aims to continue as a scientifically valuable biorepository for the biomedical research community. Over the next 5 years, we shall focus our efforts on optimizing the quality of our resource, ensuring its relevance to individual users, and seeking maximum performance for the benefit of all whom we serve.

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