MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice

Msh4 (MutS homolog 4) is a member of the mammalian mismatch repair gene fam ily whose members are involved in postreplicative DNA mismatch repair as we ll as in the control of meiotic recombination. In this report we show that MSH4 has an essential role in the control of male and female meiosis. We de monstrate that MSH4 is present in the nuclei of spermatocytes early in prop hase I and that it forms discrete foci along meiotic chromosomes during the zygotene and pachytene stages of meiosis. Disruption of the Msh4 gene in m ice results in male and female sterility due to meiotic failure. Although m eiosis is initiated in Msh4 mutant male and female mice, as indicated by th e chromosomal localization of RAD51 and COR1 during leptonema/zygonema, the chromosomes fail to undergo normal pairing. Our results show that MSH4 loc alization on chromosomes during the early stages of meiosis is essential fo r normal chromosome synapsis in prophase I and that it acts in the same pat hway as MSH5.