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Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice

Abstract

We targeted the locus encoding the cyclin-dependent kinase 2 (CDK2) by homologous recombination in mouse embryonic stem (ES) cells. Embryonic fibroblasts lacking CDK2 proliferate normally and become immortal after continuous passage in culture. Elimination of a conditional Cdk2 allele in immortal cells does not have a significant effect on proliferation. Cdk2−/− mice are viable and survive for up to two years, indicating that CDK2 is also dispensable for proliferation and survival of most cell types. But CDK2 is essential for completion of prophase I during meiotic cell division in male and female germ cells, an unforeseen role for this cell cycle kinase.

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Figure 1: Gene-targeting strategy.
Figure 2: Properties of Cdk2−/− MEFs.
Figure 3: Defective spermatogenesis in Cdk2−/− males.
Figure 4: Distribution of synaptonemal complex components in Cdk2+/+ and Cdk2−/− primary spermatocytes.
Figure 5: Defective germ cell development in Cdk2−/− females.
Figure 6: Distribution of synaptonemal complex components in Cdk2+/+ and Cdk2−/− oocytes.

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Acknowledgements

We thank P. Sicinski and B. Amati for communicating results before publication and for discussions; C. Gómez, M. Riffo, M. Muñoz, M. San Román, R. Villar and R. González for technical assistance; J.M. Buesa, F. Roncal, L. Gómez and R. Fernández for generating SMC3, SCP1 and SYCP3 antibodies; and G.C. Enders and G. Roy for GCNA1 and human autoimmune sera, respectively. The support provided by the Immunohistochemistry and Animal Facility Units of the Centro Nacional de Investigaciones Oncológicas is also greatly appreciated. The early phases of this work were carried out at the Centro Nacional de Biotecnología. This work was supported by grants from the V Framework Program of the European Union (to M.B.) and from the Comisión Interministerial de Ciencia y Tecnología (to M.B. and to S.O.). The Department of Immunology and Oncology is supported by the Spanish Council for Scientific Research and by Pfizer.

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Correspondence to Sagrario Ortega or Mariano Barbacid.

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Ortega, S., Prieto, I., Odajima, J. et al. Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat Genet 35, 25–31 (2003). https://doi.org/10.1038/ng1232

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