Meiotic pachytene arrest in MLH1-deficient mice

Winfried Edelmann, Paula E. Cohen, Michael Kane, Kirkland Lau, Bernice E. Morrow, Samuel Bennett, Asad Umar, Thomas Kunkel, Giorgio Cattoretti, Raju Chaganti, Jeffrey W. Pollard, Richard D. Kolodner, Raju Kucherlapati

Research output: Contribution to journalArticle

449 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1125-1134
Number of pages10
JournalCell
Volume85
Issue number7
DOIs
StatePublished - Jun 28 1996

Fingerprint

Genes
DNA Mismatch Repair
Meiosis
Repair
Phenotype
Hereditary Nonpolyposis Colorectal Neoplasms
Reproductive Behavior
Prophase
Microsatellite Instability
Mutation
Estrous Cycle
Germ-Line Mutation
Cell Extracts
Growth and Development
Spermatozoa
DNA

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Edelmann, W., Cohen, P. E., Kane, M., Lau, K., Morrow, B. E., Bennett, S., ... Kucherlapati, R. (1996). Meiotic pachytene arrest in MLH1-deficient mice. Cell, 85(7), 1125-1134. https://doi.org/10.1016/S0092-8674(00)81312-4

Meiotic pachytene arrest in MLH1-deficient mice. / Edelmann, Winfried; Cohen, Paula E.; Kane, Michael; Lau, Kirkland; Morrow, Bernice E.; Bennett, Samuel; Umar, Asad; Kunkel, Thomas; Cattoretti, Giorgio; Chaganti, Raju; Pollard, Jeffrey W.; Kolodner, Richard D.; Kucherlapati, Raju.

In: Cell, Vol. 85, No. 7, 28.06.1996, p. 1125-1134.

Research output: Contribution to journalArticle

Edelmann, W, Cohen, PE, Kane, M, Lau, K, Morrow, BE, Bennett, S, Umar, A, Kunkel, T, Cattoretti, G, Chaganti, R, Pollard, JW, Kolodner, RD & Kucherlapati, R 1996, 'Meiotic pachytene arrest in MLH1-deficient mice', Cell, vol. 85, no. 7, pp. 1125-1134. https://doi.org/10.1016/S0092-8674(00)81312-4
Edelmann, Winfried ; Cohen, Paula E. ; Kane, Michael ; Lau, Kirkland ; Morrow, Bernice E. ; Bennett, Samuel ; Umar, Asad ; Kunkel, Thomas ; Cattoretti, Giorgio ; Chaganti, Raju ; Pollard, Jeffrey W. ; Kolodner, Richard D. ; Kucherlapati, Raju. / Meiotic pachytene arrest in MLH1-deficient mice. In: Cell. 1996 ; Vol. 85, No. 7. pp. 1125-1134.
@article{4b1762c7998f4e59b170ac2c381a7c9f,
title = "Meiotic pachytene arrest in MLH1-deficient mice",
abstract = "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.",
author = "Winfried Edelmann and Cohen, {Paula E.} and Michael Kane and Kirkland Lau and Morrow, {Bernice E.} and Samuel Bennett and Asad Umar and Thomas Kunkel and Giorgio Cattoretti and Raju Chaganti and Pollard, {Jeffrey W.} and Kolodner, {Richard D.} and Raju Kucherlapati",
year = "1996",
month = "6",
day = "28",
doi = "10.1016/S0092-8674(00)81312-4",
language = "English (US)",
volume = "85",
pages = "1125--1134",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",

}

TY - JOUR

T1 - Meiotic pachytene arrest in MLH1-deficient mice

AU - Edelmann, Winfried

AU - Cohen, Paula E.

AU - Kane, Michael

AU - Lau, Kirkland

AU - Morrow, Bernice E.

AU - Bennett, Samuel

AU - Umar, Asad

AU - Kunkel, Thomas

AU - Cattoretti, Giorgio

AU - Chaganti, Raju

AU - Pollard, Jeffrey W.

AU - Kolodner, Richard D.

AU - Kucherlapati, Raju

PY - 1996/6/28

Y1 - 1996/6/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=15844367099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15844367099&partnerID=8YFLogxK

U2 - 10.1016/S0092-8674(00)81312-4

DO - 10.1016/S0092-8674(00)81312-4

M3 - Article

VL - 85

SP - 1125

EP - 1134

JO - Cell

JF - Cell

SN - 0092-8674

IS - 7

ER -