A New Model for Elucidating the Genetic Mechanisms of Hybrid Male Sterility in House Mice

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PROJECT SUMMARY A major goal in evolutionary genetics is to identify the genetic variants that give rise to hybrid sterility, and to understand their mechanisms of action. Hybrid sterility is important because it maintains barriers between species in nature. The house mouse, Mus musculus, presents a unique opportunity to study the genetics of hybrid sterility due to the substantial but incomplete reproductive isolation between two subspecies (M.m.musculus and M.m.domesticus). Male offspring born to a musculus female and a domesticus male often exhibit hybrid male sterility (HMS). This phenomenon can be replicated experimentally using inbred mouse strains that are representative of each subspecies. Two major genetic factors have been shown to cause HMS, but many of the genes involved remain unknown. We recently identified a specific type of hybrid male that has the known HMS-associated QTL genotypes, yet is fertile and shows no reproductive impairment. The goals of this exploratory research project are to identify the genetic variants that rescue fertility in this hybrid, to identify the stage of spermatogenesis affected by those variants, and to identify the molecular differences between infertile and fertile hybrid males. These results will advance our understanding of evolutionary genetics, reproductive biology, and meiosis.