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Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation

Nature Genetics volume 30, pages 446–449 (2002)Cite this article

Abstract

In a wide variety of animal species, oocyte maturation is arrested temporarily at prophase of meiosis I (ref. 1). Resumption of meiosis requires activation of cyclin-dependent kinase-1 (CDK1, p34cdc2), one component of maturation-promoting factor (MPF)2,3. The dual specificity phosphatases Cdc25a, Cdc25b and Cdc25c are activators of cyclin-dependent kinases4,5,6,7,8; consequently, they are postulated to regulate cell-cycle progression in meiosis and mitosis as well as the DNA-damage response9,10,11,12. We generated Cdc25b-deficient (Cdc25b−/−) mice and found that they are viable. As compared with wildtype cells, fibroblasts from Cdc25b−/− mice grew vigorously in culture and arrested normally in response to DNA damage. Female Cdc25b−/− mice were sterile, and Cdc25b−/− oocytes remained arrested at prophase with low MPF activity. Microinjection of wildtype Cdc25b mRNA into Cdc25b−/− oocytes caused activation of MPF and resumption of meiosis. Thus, Cdc25b−/− female mice are sterile because of permanent meiotic arrest resulting from the inability to activate MPF. Cdc25b is therefore essential for meiotic resumption in female mice. Mice lacking Cdc25b provide the first genetic model for studying the mechanisms regulating prophase arrest in vertebrates.

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Figure 1: Cdc25b targeting strategy and Southern- and western-blot analysis of Cdc25b-deficient mice.
Figure 2: Nomarski images and immunofluorescent staining of wildtype and Cdc25b−/− oocytes.
Figure 3: In vitro kinase assay of MPF and MAP kinase activity in wildtype and Cdc25b−/− oocytes.

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Acknowledgements

We thank M. Hilton, B. Eagleson, C. Palancar and S. Reid for chimera production and animal husbandry; T. Copeland for production of the polyclonal N-terminal Cdc25b antibody; T. Hunter and B. Sebastian for the gift of the full-length Cdc25b cDNA clone and J. McCormick for help with flow cytometry. We are also indebted to L. Lock, J. Kervinen, A. Golden, I. Daar, G. Gopalan, L. Siracusa, M. Parsons, V. Coppola and K. Vousden for helpful discussions and critical reading of the manuscript; M. Wilson for help with manuscript preparation; and R. Frederickson for preparation of one of the figures. This work was supported in part by the National Cancer Institute, National Institutes of Health, under contract with ABL (P.J.D. and L.T.), by grants from the National Institute of Child Health and Human Development (to P.J.D. and R.M.S.), by a National Research Service Award from the National Cancer Institute (to A.J.L.) and by a National Cancer Institute Cancer Center Core Grant to the Kimmel Cancer Center.

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Author notes

  1. A. Jeannine Lincoln, Maria P. De De Miguel & Peter J. Donovan

    Present address: Kimmel Cancer Center, Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, Pennsylvania, 19107, USA

  2. Dineli Wickramasinghe

    Present address: Genentech, Inc., San Francisco, California, 94080, USA

  3. A. Jeannine Lincoln and Dineli Wickramasinghe: These authors contributed equally to this work.

Authors and Affiliations

  1. National Cancer Institute-FCRDC, Frederick, 21702, Maryland, USA

    A. Jeannine Lincoln, Dineli Wickramasinghe, Mary Ellen Palko, Maria P. De De Miguel, Lino Tessarollo & Peter J. Donovan

  2. Department of Biology, University of Pennsylvania, Philadelphia, 19104-6018, Pennsylvania, USA

    Paula Stein & Richard M. Schultz

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Correspondence to Peter J. Donovan.

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Lincoln, A., Wickramasinghe, D., Stein, P. et al. Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation. Nat Genet 30, 446–449 (2002). https://doi.org/10.1038/ng856

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