Mammalian MutS homologue 5 is required for chromosome pairing in meiosis

Nat Genet. 1999 Jan;21(1):123-7. doi: 10.1038/5075.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Pair Mismatch
  • DNA Repair
  • DNA-Binding Proteins / analysis
  • Egg Proteins / biosynthesis
  • Female
  • Fungal Proteins / physiology*
  • Humans
  • Male
  • Meiosis / genetics*
  • Meiosis / physiology
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nuclear Proteins / analysis
  • Pedigree
  • Rad51 Recombinase
  • Receptors, Cell Surface*
  • Saccharomyces cerevisiae Proteins*
  • Zona Pellucida Glycoproteins

Substances

  • DNA-Binding Proteins
  • Egg Proteins
  • Fungal Proteins
  • MSH5 protein, S cerevisiae
  • Membrane Glycoproteins
  • Nuclear Proteins
  • Receptors, Cell Surface
  • SYCP1 protein, human
  • SYCP3 protein, human
  • Saccharomyces cerevisiae Proteins
  • Sycp1 protein, mouse
  • Sycp3 protein, mouse
  • Zona Pellucida Glycoproteins
  • RAD51 protein, human
  • Rad51 Recombinase
  • Rad51 protein, mouse

Associated data

  • GENBANK/AF107352
  • GENBANK/AF107353
  • GENBANK/AF107354
  • GENBANK/AF107355
  • GENBANK/AH008149