부산대학교 도서관

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. Author summary: Inbred laboratory mouse strains are integral tools for both preclinical and basic research. However, laboratory mice capture a small fraction of the genetic diversity found in wild mouse populations, a consideration that necessarily constrains the scope of possible discovery in studies restricted to lab mice. Further, laboratory mice were developed through programs of intense artificial selection for increased breeding performance, docility, and other traits of interest. Consequently, the genetic control of many complex traits in lab mice may not accurately reflect the mechanisms of their regulation in nature. To overcome these limitations, we developed a new inbred mouse strain resource founded from wild-caught mice subject to minimal laboratory selection. We show that strains in this "Nachman panel" harbor millions of genetic variants absent from current laboratory mouse models, including predicted deleterious alleles and gene-spanning structural variants. Paralleling this genetic diversity, we show that Nachman strains capture striking phenotypic variation across a multitude of disease-relevant biochemical, neurobehavioral, physiological, morphological, and metabolic traits, expanding the range of trait variation recovered in lab strains alone. Overall, our strain survey emphasizes the collective potential of the Nachman strains to advance discoveries into multiple disease areas and basic biology. [ABSTRACT FROM AUTHOR]