Mammalian MutS homologue 5 is required for chromosome pairing in meiosis

Winfried Edelmann, Paula E. Cohen, Burkhard Kneitz, Nena Winand, Marie Lia, Joerg Heyer, Richard Kolodner, Jeffrey W. Pollard, Raju Kucherlapati

Research output: Contribution to journalArticle

286 Citations (Scopus)

Abstract

MSH5 (MutS homologue 5) is a member of a family of proteins known to be involved in DNA mismatch repair. Germline mutations in MSH2, MLH1 and GTBP (also known as MSH6) cause hereditary non-polyposis colon cancer (HNPCC) or Lynch syndrome. Inactivation of Msh2, Mlh1, Gtmbp (also known as Msh6) or Pms2 in mice leads to hereditary predisposition to intestinal and other cancers. Early studies in yeast revealed a role for some of these proteins, including Msh5, in meiosis. Gene targeting studies in mice confirmed roles for Mlh1 and Pms2 in mammalian meiosis. To assess the role of Msh5 in mammals, we generated and characterized mice with a null mutation in Msh5. Msh5(-/-) mice are viable but sterile. Meiosis in these mice is affected due to the disruption of chromosome pairing in prophase I. We found that this meiotic failure leads to a diminution in testicular size and a complete loss of ovarian structures. Our results show that normal Msh5 function is essential for meiotic progression and, in females, gonadal maintenance.

Original languageEnglish (US)
Pages (from-to)123-127
Number of pages5
JournalNature Genetics
Volume21
Issue number1
DOIs
StatePublished - Jan 1999

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Chromosome Pairing
Meiosis
Meiotic Prophase I
Intestinal Neoplasms
Hereditary Nonpolyposis Colorectal Neoplasms
DNA Mismatch Repair
Gene Targeting
Germ-Line Mutation
Colonic Neoplasms
Mammals
Proteins
Yeasts
Maintenance
Mutation

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Edelmann, W., Cohen, P. E., Kneitz, B., Winand, N., Lia, M., Heyer, J., ... Kucherlapati, R. (1999). Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. Nature Genetics, 21(1), 123-127. https://doi.org/10.1038/5075

Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. / Edelmann, Winfried; Cohen, Paula E.; Kneitz, Burkhard; Winand, Nena; Lia, Marie; Heyer, Joerg; Kolodner, Richard; Pollard, Jeffrey W.; Kucherlapati, Raju.

In: Nature Genetics, Vol. 21, No. 1, 01.1999, p. 123-127.

Research output: Contribution to journalArticle

Edelmann, W, Cohen, PE, Kneitz, B, Winand, N, Lia, M, Heyer, J, Kolodner, R, Pollard, JW & Kucherlapati, R 1999, 'Mammalian MutS homologue 5 is required for chromosome pairing in meiosis', Nature Genetics, vol. 21, no. 1, pp. 123-127. https://doi.org/10.1038/5075
Edelmann, Winfried ; Cohen, Paula E. ; Kneitz, Burkhard ; Winand, Nena ; Lia, Marie ; Heyer, Joerg ; Kolodner, Richard ; Pollard, Jeffrey W. ; Kucherlapati, Raju. / Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. In: Nature Genetics. 1999 ; Vol. 21, No. 1. pp. 123-127.
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