Into the Wild: A novel wild-derived inbred strain resource expands the genomic and phenotypic diversity of laboratory mouse models.
Autor: | Dumont BL; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America.; Graduate School of Biomedical Sciences, Tufts University, Boston, Massachusetts, United States of America.; Graduate School of Biomedical Science and Engineering, The University of Maine, Orono, Maine, United States of America., Gatti DM; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America., Ballinger MA; Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, New York, United States of America., Lin D; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America., Phifer-Rixey M; Department of Biology, Drexel University, Philadelphia, Pennsylvania, United States of America., Sheehan MJ; Department of Neurobiology and Behavior, Cornell University, Ithaca, New York, United States of America., Suzuki TA; College of Health Solutions and Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, Arizona, United States of America., Wooldridge LK; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America., Frempong HO; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America.; Graduate School of Biomedical Science and Engineering, The University of Maine, Orono, Maine, United States of America., Lawal RA; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America., Churchill GA; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America.; Graduate School of Biomedical Sciences, Tufts University, Boston, Massachusetts, United States of America.; Graduate School of Biomedical Science and Engineering, The University of Maine, Orono, Maine, United States of America., Lutz C; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America., Rosenthal N; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America.; Graduate School of Biomedical Sciences, Tufts University, Boston, Massachusetts, United States of America.; Graduate School of Biomedical Science and Engineering, The University of Maine, Orono, Maine, United States of America.; National Heart and Lung Institute, Imperial College London, London, United Kingdom., White JK; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America., Nachman MW; Department of Integrative Biology, Museum of Vertebrate Zoology, and Center for Computational Biology, University of California, Berkeley, Berkeley, California, United States of America. |
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Jazyk: | angličtina |
Zdroj: | PLoS genetics [PLoS Genet] 2024 Apr 10; Vol. 20 (4), pp. e1011228. Date of Electronic Publication: 2024 Apr 10 (Print Publication: 2024). |
DOI: | 10.1371/journal.pgen.1011228 |
Abstrakt: | 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-caught Mus 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 mouse reference, with 42.5% of variants in the Nachman strain genomes absent from current classical inbred mouse strain panels. We phenotyped the Nachman strains on a customized pipeline to assess the scope of disease-relevant neurobehavioral, biochemical, physiological, metabolic, and morphological trait variation. The Nachman strains exhibit significant inter-strain variation in >90% of 1119 surveyed traits and expand the range of phenotypic diversity captured in classical inbred strain panels. These novel wild-derived inbred mouse strain resources are set to empower new discoveries in both basic and preclinical research. Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2024 Dumont et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
Databáze: | MEDLINE |
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