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Condensin dysfunction is a reproductive isolating barrier in mice

Reproductive isolation occurs when the genomes of two populations accumulate genetic incompatibilities that prevent inter-breeding. Cell biological understanding of such hybrid incompatibility is limited, especially for hybrid female sterility. Here we find that species divergence in condensin regulation and centromere organization between two mouse species, Mus musculus and Mus spretus, drives chromosome de-condensation and mis-segregation in their F1 hybrid oocytes, reducing female fertility. The chromosome condensation defects in hybrid oocytes were especially prominent at Mus musculus centromeres due to their highly abundant major satellite DNA, leading to species-specific chromosome mis-segregation. This study provides the first mechanistic insights into hybrid incompatibility in female meiosis and demonstrates that condensin mis-regulation can be a reproductive isolating barrier in mammals.