A Mutation in Mtap2 Is Associated with Arrest of Mammalian Spermatocytes before the First Meiotic Division

In spite of evolutionary conservation of meiosis, many of the genes that control mammalian meiosis are still unknown. We report here that the ENU-induced repro4 mutation, identified in a screen to uncover genes that control mouse meiosis, causes failure of spermatocytes to exit meiotic prophase I via the G2/MI transition. Major events of meiotic prophase I occurred normally in affected spermatocytes and known regulators of the meiotic G2/MI transition were present and functional. Deep sequencing of mutant DNA revealed a mutation located in an intron of the Mtap2 gene, encoding microtubule-associated protein 2, and levels of Mtap2 transcript were reduced in mutant testes. This evidence implicates MTAP2 as required directly or indirectly for completion of meiosis and normal spermatogenesis in mammals.