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PubMed · 14561402

Cdk2 knockout mice are viable.

Cyril Berthet·Eiman Aleem·Vincenzo Coppola·Lino Tessarollo·Philipp Kaldis
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Abstract

BACKGROUND: Cyclin-dependent kinases (Cdks) and their cyclin regulatory subunits control cell growth and division. Cdk2/cyclin E complexes are thought to be required because they phosphorylate the retinoblastoma protein and drive cells through the G1/S transition into the S phase of the cell cycle. In addition, Cdk2 associates with cyclin A, which itself is essential for cell proliferation during early embryonic development. RESULTS: In order to study the functions of Cdk2 in vivo, we generated Cdk2 knockout mice. Surprisingly, these mice are viable, and therefore Cdk2 is not an essential gene in the mouse. However, Cdk2 is required for germ cell development; both male and female Cdk2(-/-) mice are sterile. Immunoprecipitates of cyclin E1 complexes from Cdk2(-/-) spleen extracts displayed no activity toward histone H1. Cyclin A2 complexes were active in primary mouse embryonic fibroblasts (MEFs), embryo extracts and in spleen extracts from young animals. In contrast, there was little cyclin A2 kinase activity in immortalized MEFs and spleen extracts from adult animals. Cdk2(-/-) MEFs proliferate but enter delayed into S phase. Ectopic expression of Cdk2 in Cdk2(-/-) MEFs rescued the delayed entry into S phase. CONCLUSIONS: Although Cdk2 is not an essential gene in the mouse, it is required for germ cell development and meiosis. Loss of Cdk2 affects the timing of S phase, suggesting that Cdk2 is involved in regulating progression through the mitotic cell cycle.

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AnimalsCDC2-CDC28 KinasesCell CycleChromosome MappingCyclin ACyclin ECyclin-Dependent Kinase 2FibroblastsGene Expression ProfilingGerm CellsGonadsHistological TechniquesHistonesMeiosisMiceMice, KnockoutMolecular Probe TechniquesPrecipitin TestsSpleenComparative StudyJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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Cyril Berthet, Eiman Aleem, Vincenzo Coppola, Lino Tessarollo, Philipp Kaldis. 2003-10-14. Cdk2 knockout mice are viable.. https://doi.org/10.1016/j.cub.2003.09.024

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