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Vol. 14, No. 9, pp. 1085-1097, May 1, 2000
Departments of 1 Cell Biology, 2 Developmental and
Molecular Biology, and 4 Molecular Genetics, Albert Einstein
College of Medicine, The Bronx, New York 10461 USA;
3 Ludwig Institute for Cancer Research, LaJolla, California 92093 USA
Msh4 (MutS homolog 4) is a member of the mammalian mismatch
repair gene family whose members are involved in postreplicative DNA
mismatch repair as well as in the control of meiotic recombination. In
this report we show that MSH4 has an essential role in the control of
male and female meiosis. We demonstrate that MSH4 is present in the
nuclei of spermatocytes early in prophase I and that it forms discrete
foci along meiotic chromosomes during the zygotene and pachytene stages
of meiosis. Disruption of the Msh4 gene in mice results in male
and female sterility due to meiotic failure. Although meiosis is
initiated in Msh4 mutant male and female mice, as indicated by
the chromosomal localization of RAD51 and COR1 during
leptonema/zygonema, the chromosomes fail to undergo normal pairing. Our results show that MSH4 localization on chromosomes during the early stages of meiosis is essential for normal chromosome synapsis in prophase I and that it acts in the same pathway as MSH5.
[Key Words: Mismatch repair; meiosis; chromosome synapsis; recombination; germ cell]
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