MoG+: a database of genomic variations across three mouse subspecies for biomedical research

Abstract

Laboratory mouse strains have mosaic genomes derived from at least three major subspecies that are distributed in Eurasia. Here, we describe genomic variations in ten inbred strains: Mus musculus musculus-derived BLG2/Ms, NJL/Ms, CHD/Ms, SWN/Ms, and KJR/Ms; M. m. domesticus-derived PGN2/Ms and BFM/Ms; M. m. castaneus-derived HMI/Ms; and JF1/Ms and MSM/Ms, which were derived from a hybrid between M. m. musculus and M. m. castaneus. These strains were established by Prof. Moriwaki in the 1980s and are collectively named the “Mishima Battery”. These strains show large phenotypic variations in body size and in many physiological traits. We resequenced the genomes of the Mishima Battery strains and performed a comparative genomic analysis with dbSNP data. More than 81 million nucleotide coordinates were identified as variant sites due to the large genetic distances among the mouse subspecies; 8,062,070 new SNP sites were detected in this study, and these may underlie the large phenotypic diversity observed in the Mishima Battery. The new information was collected in a reconstructed genome database, termed MoG+ that includes new application software and viewers. MoG+ intuitively visualizes nucleotide variants in genes and intergenic regions, and amino acid substitutions across the three mouse subspecies. We report statistical data from the resequencing and comparative genomic analyses and newly collected phenotype data of the Mishima Battery, and provide a brief description of the functions of MoG+, which provides a searchable and unique data resource of the numerous genomic variations across the three mouse subspecies. The data in MoG+ will be invaluable for research into phenotype-genotype links in diverse mouse strains.

Phenogenomic resources immortalized in a panel of wild-derived strains of five species of house mice

“…Possibly because of long-term artificial selection in captivity, CLS outperform WDS in terms of reproductive parameters (Table 4), which highlights their suitability as models for biomedical research. The phenotypic differentiation between WDS and CLS observed here in congruent with the study of Takada et al 72 comparing 10 WDS derived from domesticus , castaneus , and molossinus subspecies and one CLS (C57BL/6). In that study, significant differences were found in 62—68% of 21 measured morphological and physiological traits 72 .…”

“…The phenotypic differentiation between WDS and CLS observed here in congruent with the study of Takada et al 72 comparing 10 WDS derived from domesticus , castaneus , and molossinus subspecies and one CLS (C57BL/6). In that study, significant differences were found in 62—68% of 21 measured morphological and physiological traits 72 .…”

“…In summary, the genetic data corroborate previous analyses that have found higher diversity in wild mice compared with CLS e.g. 9,36,53,72,73 . Simultaneously, Slx and Sly CN, along with the numerous significant differences in external morphology and reproductive characteristics, suggest CLS are not simply domesticated representatives of M. m. domesticus , despite the overwhelming portion of domesticus genome they carry 9 .…”

Two Loci Contribute to Age-Related Hearing Loss Resistance in the Japanese Wild-Derived Inbred MSM/Ms Mice

“…We extracted 64,664 (57,165 SNPs, 3038 insertions, and 4461 deletions) and 48,295 (42,018 SNPs, 2626 insertions, and 3651 deletions) polymorphisms between B6 and MSM strains in B6.MSM- ahl3 /2 and - ahl10 congenic regions, respectively, using the MoG+ database [ 27 ]. The ahl3 /2 and ahl10 regions harbor 27 and 36 protein-coding genes, respectively.…”

Phylogeographic study using nuclear genome sequences of <i>Asip</i> to infer the origins of ventral fur color variation in the house mouse <i>Mus musculus</i>

“…The color of the coat, in particular the ventral fur color, often differs depending on the geographic location in M. musculus (Marshall, 1998;Slábová and Frynta, 2007;Lai et al, 2008) and has been used as a diagnostic marker in the mouse (Schwarz and Schwarz, 1943;Marshall, 1998). The hair color of this species, which is currently divided into three subspecies groups, i.e., M. m. castaneus (CAS: southern Asia, Southeast Asia and southern China), M. m. domesticus (DOM: western Asia and western Europe) and M. m. musculus (MUS: northern Eurasia) (e.g., Suzuki et al, 2013;Takada et al, 2013), varies both within and between the subspecies (Takada et al, 2021). An understanding of the genetic background of phenotypic variation would allow observations of coat color variation in wild populations to provide insights into phylogenetic background (Kambe et al, 2011;Suzuki, 2013;Kodama et al, 2015;Sasamori et al, 2017;Marín et al, 2018).…”