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Mei1 is epistatic to Dmc1 during mouse meiosis

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Abstract

The Mei1m1Jcs allele contains a point mutation in a novel gene required for normal meiosis in male and female mice. We previously hypothesized that Mei1 is likely required for the formation of genetically programmed double-strand breaks (DSBs), the initiating event of meiotic recombination because in mutant spermatocytes (1) RAD51 foci are greatly reduced at zygonema; (2) RAD51 foci can be restored by cisplatin-induced DNA damage; and (3) phosphorylated H2AX is greatly reduced at leptonema. If this hypothesis is correct, Mei1 would act upstream of genes required for repair of DSBs by homologous recombination. To test this, we examined meiosis in Meim1Jcs/Mei1m1Jcs (Mei1-/-) and Dmc1tm1Jcs/Dmc1tm1Jcs (Dmc1-/-) mice and mice homozygous at both loci (Dmc1-/- Mei1-/-), exploiting the fact that oogenesis is much more severely affected by the absence of DMC1 than by the absence of MEI1. The phenotypes of both male and female double mutants were identical to that of Mei1-/- animals. Therefore, Mei1 can be positioned upstream of Dmc1 in the genetic pathway that operates during mammalian meiosis. Furthermore, this epistatic interaction provides additional evidence in support of the hypothesis that Mei1 is required for the initiating events of meiotic recombination.

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Acknowledgements

We acknowledge the histology services at the Jackson Laboratory and Drs. C. Heyting (Wageningen University, Wageningen, Netherlands), C. Ingles (University of Toronto, Toronto, Canada), and M.A. Handel (The Jackson Laboratory) for kindly providing some of the antibodies used in this study. We also thank M.A. Handel and the reviewers for their insightful critical comments.

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Authors and Affiliations

  1. The Jackson Laboratory, Bar Harbor, ME, 04609, USA

    Laura G. Reinholdt

  2. Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, VRT9014A, Ithaca, NY, 14853, USA

    John C. Schimenti

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  1. Laura G. Reinholdt
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  2. John C. Schimenti
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Correspondence to John C. Schimenti.

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Communicated by E.A. Nigg

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Reinholdt, L.G., Schimenti, J.C. Mei1 is epistatic to Dmc1 during mouse meiosis. Chromosoma 114, 127–134 (2005). https://doi.org/10.1007/s00412-005-0346-4

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  • DOI: https://doi.org/10.1007/s00412-005-0346-4

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