For decades, the mouse has been the premier animal model for studies of human disease, providing the opportunity to explore experimental questions that are intractable for direct study in humans. As a result, key insights have been obtained for a variety of clinical conditions. Spurred by advances in technology and international efforts to systematically knock out all of the protein coding genes in the genome, the number of genetically engineered mice has expanded rapidly in the past 20 years. The responsibility for maintenance and distribution of mutant mice was initially placed on individual investigators, which was a tremendous burden in terms of cost, labor and space. In 1999, the NIH recognized the need for a resource to protect the investment in mutant mouse strains and ensure open access to all biomedical researchers and established the Mutant Mouse Regional Resource Centers (MMRRC). Since 1999, the central goal of the MMRRC-UNC has been to work collectively with MMRRC consortium partners to develop and maintain high standards for importation, rederivation, cryopreservation, and distribution of mutant mouse strains to biomedical investigators. The MMRRC- UNC will continue to contribute to the goals of the Consortium in the next project period by implementing the following Specific Aims devoted to continuing its successful role as a cryoarchive and distribution center and incorporating research goals that synergize with and extend the value of the resource: 1) Streamline and improve operating procedures to increase importation, distribution, and cryoarchiving of mouse strains. 2) Establish a comprehensive cryoarchive for the Collaborative Cross (CC) resource. 3) Develop and disseminate computational tools for mouse genotyping and genomics research, which will enhance phenotypic reproducibility. 4) Examine the effect of paternal age and epigenetics on mutation rate.

Public Health Relevance

Genetically engineered mouse models provide a tractable system for studying human development and disease. The knowledge gained has the potential for dramatically improving public health. The MMRRC-UNC imports, archives and distributes mouse strains to the scientific community to protect and provide efficient access to this valuable resource. In addition, the MMRRC-UNC has developed comprehensive genotyping tools that aid in understanding the effect of genetic background on phenotypic variability.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Animal (Mammalian and Nonmammalian) Model, and Animal and Biological Materials Resource Cooperative Agreements (U42)
Project #
5U42OD010924-19
Application #
9418132
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mirochnitchenko, Oleg
Project Start
1999-09-30
Project End
2020-02-28
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
19
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Genetics
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Morgan, Andrew P; Pardo-Manuel de Villena, Fernando (2017) Sequence and Structural Diversity of Mouse Y Chromosomes. Mol Biol Evol 34:3186-3204
Srivastava, Anuj; Morgan, Andrew P; Najarian, Maya L et al. (2017) Genomes of the Mouse Collaborative Cross. Genetics 206:537-556
Morgan, Andrew P; Fu, Chen-Ping; Kao, Chia-Yu et al. (2015) The Mouse Universal Genotyping Array: From Substrains to Subspecies. G3 (Bethesda) 6:263-79
Morgan, Andrew P (2015) argyle: An R Package for Analysis of Illumina Genotyping Arrays. G3 (Bethesda) 6:281-6
Fedoriw, Andrew M; Menon, Debashish; Kim, Yuna et al. (2015) Key mediators of somatic ATR signaling localize to unpaired chromosomes in spermatocytes. Development 142:2972-80
Morgan, Andrew P; Welsh, Catherine E (2015) Informatics resources for the Collaborative Cross and related mouse populations. Mamm Genome 26:521-39
Rogala, Allison R; Morgan, Andrew P; Christensen, Alexis M et al. (2014) The Collaborative Cross as a resource for modeling human disease: CC011/Unc, a new mouse model for spontaneous colitis. Mamm Genome 25:95-108
Mu, Weipeng; Starmer, Joshua; Fedoriw, Andrew M et al. (2014) Repression of the soma-specific transcriptome by Polycomb-repressive complex 2 promotes male germ cell development. Genes Dev 28:2056-69
Gray, Jeffrey E; Starmer, Joshua; Lin, Vivian S et al. (2013) Mitochondrial hydrogen peroxide and defective cholesterol efflux prevent in vitro fertilization by cryopreserved inbred mouse sperm. Biol Reprod 89:17

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