Mouse consomic strains: Exploiting genetic divergence between <i>Mus m. musculus</i> and <i>Mus m. domesticus</i> subspecies

Gregorová, Soňa; Divina, Petr; Storchová, Radka; Trachtulec, Zdeněk; Fotopulosová, Vladana; Svenson, Karen L.; Donahue, Leah Rae; Paigen, Beverly; Forejt, Jiřı́

doi:10.1101/gr.7160508

Cited by 123 publications

(127 citation statements)

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“…In hybrid males, sterility is more common when M. m. musculus is the mother (Britton-Davidian et al 2005;Good et al 2008b;Vyskočilová et al 2009). The role for the M. m. musculus X chromosome suggested by these observations has been confirmed through backcrosses (Storchová et al 2004) and chromosomal introgression studies (Good et al 2008a;Gregorová et al 2008). Reduced gene flow of X-linked loci across the hybrid zone (Tucker et al 1992;Dod et al 1993;Munclinger et al 2002;Payseur et al 2004;Dod et al 2005;Macholán et al 2007) raises the possibility that this chromosome also confers hybrid male sterility in natural populations.…”

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confidence: 70%

“…In addition, chromosome substitution lines that carry either chromosome 10 or 11 from M. m. musculus PWD on the genomic background of a classical inbred strain derived primarily from M. m. domesticus (C57BL/6J) show reduced fertility (Gregorová et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Backcrosses between M. m. domesticus and Mus musculus molossinus (a hybrid between M. m. musculus and Mus musculus castaneus) have identified several autosomal QTL that affect hybrid sterility when the entire M. m. molossinus X chromosome is present on the M. m. domesticus genetic background (Oka et al 2007). Substituting M. m. musculus chromosomes 10 or 11 onto a mostly M. m. domesticus background (C57BL/6J inbred line) strongly reduces litter size (Gregorová et al 2008). Finally, some autosomal loci show reduced introgression across the European hybrid zone (Macholán et al 2007;Teeter et al 2008Teeter et al , 2010.…”

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Genetic Dissection of a Key Reproductive Barrier Between Nascent Species of House Mice

et al. 2011

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Reproductive isolation between species is often caused by deleterious interactions among loci in hybrids. Finding the genes involved in these incompatibilities provides insight into the mechanisms of speciation. With recently diverged subspecies, house mice provide a powerful system for understanding the genetics of reproductive isolation early in the speciation process. Although previous studies have yielded important clues about the genetics of hybrid male sterility in house mice, they have been restricted to F 1 sterility or incompatibilities involving the X chromosome. To provide a more complete characterization of this key reproductive barrier, we conducted an F 2 intercross between wild-derived inbred strains from two subspecies of house mice, Mus musculus musculus and Mus musculus domesticus. We identified a suite of autosomal and X-linked QTL that underlie measures of hybrid male sterility, including testis weight, sperm density, and sperm morphology. In many cases, the autosomal loci were unique to a specific sterility trait and exhibited an effect only when homozygous, underscoring the importance of examining reproductive barriers beyond the F 1 generation. We also found novel two-locus incompatibilities between the M. m. musculus X chromosome and M. m. domesticus autosomal alleles. Our results reveal a complex genetic architecture for hybrid male sterility and suggest a prominent role for reproductive barriers in advanced generations in maintaining subspecies integrity in house mice.

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confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Genetic Dissection of a Key Reproductive Barrier Between Nascent Species of House Mice

et al. 2011

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“…It is important to bear in mind, however, that a large X effect has not yet been demonstrated in mice, and this calculation is thus very rough. Two recent studies constructed large sets of consomic lines substituting individual chromosomes from M. m. molossinus (MSM/Ms; Takada et al 2008) or M. musculus (PWK/Ph; Gregorová et al 2008) on the background of the classic laboratory strain C57BL/6J. Both experiments uncovered putative incompatibilities involving most autosomes, with deleterious effects on strain reproduction and viability.…”

Section: Discussionmentioning

confidence: 99%

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

Good¹,

2008

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The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome.

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“…Recently, Forejt and colleagues constructed another set of inter-subspecific consomic strains, using M. m. musculusderived PWD/Ph strain as the donor and B6 as the host strain (Gregorová et al 2008). Phenotyping of these consomic strains also detected a number of QTLs.…”

Section: Discussionmentioning

confidence: 99%

Mouse inter-subspecific consomic strains for genetic dissection of quantitative complex traits

Takada

Mita²,

Maeno³

et al. 2008

Genome Res.

101

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Consomic strains, also known as chromosome substitution strains, are powerful tools for assigning polygenes that control quantitative complex traits to specific chromosomes. Here, we report generation of a full set of mouse consomic strains, in which each chromosome of the common laboratory strain C57BL/6J (B6) is replaced by its counterpart from the inbred strain MSM/Ms, which is derived from Japanese wild mouse, Mus musculus molossinus. The genome sequence of MSM/Ms is divergent from that of B6, whose genome is predominantly derived from Western European wild mouse, Mus musculus domesticus. MSM/Ms exhibits a number of quantitative complex traits markedly different from those of B6. We systematically determined phenotypes of these inter-subspecific consomic strains, focusing on complex traits related to reproduction, growth, and energy metabolism. We successfully detected more than 200 statistically significant QTLs affecting 26 traits. Furthermore, phenotyping of the consomic strains revealed that the measured values for quantitative complex traits often far exceed the range between B6 host and MSM/Ms donor strains; this may result from segregation of alleles or nonadditive interactions among multiple genes derived from the two mouse subspecies (that is, epistasis). Taken together, the results suggest that the inter-subspecific consomic strains will be very useful for identification of latent genetic components underlying quantitative complex traits.

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Mouse consomic strains: Exploiting genetic divergence between Mus m. musculus and Mus m. domesticus subspecies

Cited by 123 publications

References 48 publications

Genetic Dissection of a Key Reproductive Barrier Between Nascent Species of House Mice

Genetic Dissection of a Key Reproductive Barrier Between Nascent Species of House Mice

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

Mouse inter-subspecific consomic strains for genetic dissection of quantitative complex traits

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