Document Type

Article

Publication Date

4-1-2024

Keywords

JMG, SS1, Animals, Mice, Phenotype, Mice, Inbred Strains, Genetic Variation, Genomics, Animals, Wild, Genome, Polymorphism, Single Nucleotide, Haplotypes, Whole Genome Sequencing

JAX Source

PLoS Genet. 2024;20(4):e1011228.

ISSN

1553-7404

PMID

38598567

DOI

https://doi.org/10.1371/journal.pgen.1011228

Grant

Importation, whole-genome sequencing, and phenotyping were supported by a JAX Director’s Innovation Fund Award to B.L.D., G.C., N.R., C.L, and J.K.W. Genome sequencing of the two Tucson strains was partially supported by JAX Scholar Funds to R.A.L. B.L.D. is supported by a Maximizing Investigators’ Research Award from the National Institute of General Medical Sciences (GM133415; https://www.nigms.nih.gov/).

Abstract

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.

Comments

© 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

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