Meiotic pachytene arrest in MLH1-deficient mice

Cell. 1996 Jun 28;85(7):1125-34. doi: 10.1016/s0092-8674(00)81312-4.


Germ line mutations in DNA mismatch repair genes including MLH1 cause hereditary nonpolyposis colon cancer. To understand the role of MLH1 in normal growth and development, we generated mice that have a null mutation of this gene. Mice homozygous for this mutation show a replication error phenotype, and extracts of these cells are deficient in mismatch repair activity. Homozygous mutant males show normal mating behavior but have no detectable mature sperm. Examination of meiosis in these males reveals that the cells enter meiotic prophase and arrest at pachytene. Homozygous mutant females have normal estrous cycles and reproductive and mating behavior but are infertile. The phenotypes of the mlh1 mutant mice are distinct from those deficient in msh2 and pms2. The different phenotypes of the three types of mutant mice suggest that these three genes may have independent functions in mammalian meiosis.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • DNA Repair / genetics
  • Female
  • Fungal Proteins / genetics*
  • Germ-Line Mutation / genetics*
  • Male
  • Meiosis / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microsatellite Repeats / genetics
  • Molecular Sequence Data
  • MutL Protein Homolog 1
  • Oocytes / physiology
  • Reproduction / genetics
  • Saccharomyces cerevisiae Proteins


  • Adaptor Proteins, Signal Transducing
  • Fungal Proteins
  • MLH1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • MutL Protein Homolog 1

Associated data

  • GENBANK/U59881
  • GENBANK/U59882
  • GENBANK/U59883
  • GENBANK/U59884
  • GENBANK/U60872