Into the Wild: A novel wild-derived inbred strain resource expands the genomic and phenotypic diversity of laboratory mouse models

by Beth L. Dumont, Daniel M. Gatti, Mallory A. Ballinger, Dana Lin, Megan Phifer-Rixey, Michael J. Sheehan, Taichi A. Suzuki, Lydia K. Wooldridge, Hilda Opoku Frempong, Raman Akinyanju Lawal, Gary A. Churchill, Cathleen Lutz, Nadia Rosenthal, Jacqueline K. White, Michael W. Nachman The laboratory mouse has served as the premier animal model system for both basic and preclinical investigations for over a century. However, laboratory mice capture only a subset of the genetic variation found in wild mouse populations, ultimately limiting the potential of classical inbred strains to uncover phenotype-associated variants and pathways. Wild mouse populations are reservoirs of genetic diversity that could facilitate the discovery of new functional and disease-associated alleles, but the scarcity of commercially available, well-characterized wild mouse strains limits their broader adoption in biomedical research. To overcome this barrier, we have recently developed, sequenced, and phenotyped a set of 11 inbred strains derived from wild-caughtMus musculus domesticus. Each of these “Nachman strains” immortalizes a unique wild haplotype sampled from one of five environmentally distinct locations across North and South America. Whole genome sequence analysis reveals that each strain carries between 4.73–6.54 million single nucleotide differences relative to the GRCm39 mous e reference, with 42.5% of variants in the Nachman strain genomes absent from current classical inbred mouse ...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research