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

Burkhard Kneitz, Paula E. Cohen, Elena Avdievich, Liyin Zhu, Michael F. Kane, Harry Hou, Richard D. Kolodner, Raju Kucherlapati, Jeffrey W. Pollard, Winfried Edelmann

Research output: Contribution to journalArticle

320 Scopus citations

Abstract

Msh4 (MutS homolog 4) is a member of the mammalian mismatch repair gene family whose members are involved in postreplicative DNA mismatch repair as well 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 demonstrate that MSH4 is present in the nuclei of spermatocytes early in prophase I and that it forms discrete loci along meiotic chromosomes during the zygotene and pachytene stages of meiosis. Disruption of the Msh4 gene in mice results in male and female sterility due to meiotic failure. Although meiosis is initiated in Msh4 mutant male and female mice, as indicated by the chromosomal localization of RAD51 and COR1 during leptonema/zygonema, the chromosomes fail to undergo normal pairing. Our results show that MSH4 localization on chromosomes during the early stages of meiosis is essential for normal chromosome synapsis in prophase I and that it acts in the same pathway as MSH5.

Original languageEnglish (US)
Pages (from-to)1085-1097
Number of pages13
JournalGenes and Development
Volume14
Issue number9
StatePublished - May 1 2000

Keywords

  • Chromosome synapsis
  • Germ cell
  • Meiosis
  • Mismatch repair
  • Recombination

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Kneitz, B., Cohen, P. E., Avdievich, E., Zhu, L., Kane, M. F., Hou, H., Kolodner, R. D., Kucherlapati, R., Pollard, J. W., & Edelmann, W. (2000). MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice. Genes and Development, 14(9), 1085-1097.