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

doi:10.1038/5075

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

Cell Biology

Research output: Contribution to journal › Article › peer-review

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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 language	English (US)
Pages (from-to)	123-127
Number of pages	5
Journal	Nature Genetics
Volume	21
Issue number	1
DOIs	https://doi.org/10.1038/5075
State	Published - Jan 1999

ASJC Scopus subject areas

Genetics

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10.1038/5075

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@article{f90840708ca745b78ef1d7624be4a6cd,

title = "Mammalian MutS homologue 5 is required for chromosome pairing in meiosis",

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.",

author = "Winfried Edelmann and Cohen, {Paula E.} and Burkhard Kneitz and Nena Winand and Marie Lia and Joerg Heyer and Richard Kolodner and Pollard, {Jeffrey W.} and Raju Kucherlapati",

note = "Funding Information: We thank the following colleagues for generously providing antibodies and advice: P. Moens, B. Spyropoulos and G. Enders. The expert technical assistance of H. Hou Jr, L. Zhu and members of the AECOM Analytical Imaging Facility (F. Maculuso, L. Gunther and C. Marks) is appreciated. We also thank S. Shenoy for training and help with the CCD imaging system. This work was supported by NIH grants (CA 76329 to W.E.; CA 67944 and NO1-CN-65031 to R.K.; CA 44704 to R.D.K.), the American Cancer Society (R.K.) and a Cancer Center grant to AECOM (CA13330).",

year = "1999",

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doi = "10.1038/5075",

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T1 - Mammalian MutS homologue 5 is required for chromosome pairing in meiosis

AU - Edelmann, Winfried

AU - Cohen, Paula E.

AU - Kneitz, Burkhard

AU - Winand, Nena

AU - Lia, Marie

AU - Heyer, Joerg

AU - Kolodner, Richard

AU - Pollard, Jeffrey W.

AU - Kucherlapati, Raju

N1 - Funding Information: We thank the following colleagues for generously providing antibodies and advice: P. Moens, B. Spyropoulos and G. Enders. The expert technical assistance of H. Hou Jr, L. Zhu and members of the AECOM Analytical Imaging Facility (F. Maculuso, L. Gunther and C. Marks) is appreciated. We also thank S. Shenoy for training and help with the CCD imaging system. This work was supported by NIH grants (CA 76329 to W.E.; CA 67944 and NO1-CN-65031 to R.K.; CA 44704 to R.D.K.), the American Cancer Society (R.K.) and a Cancer Center grant to AECOM (CA13330).

PY - 1999/1

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N2 - 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.

AB - 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.

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Mammalian MutS homologue 5 is required for chromosome pairing in meiosis

Abstract

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