Cdk2 knockout mice are viable.
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.
Berthet
Cyril
C
Regulation of Cell Growth Laboratory, National Cancer Institute, Building 560, 1050 Boyles St., Frederick, MD 21702-1201, USA.
Aleem
Eiman
E
Coppola
Vincenzo
V
Tessarollo
Lino
L
Kaldis
Philipp
P
D000818:Animals; D042846:CDC2-CDC28 Kinases / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D002874:Chromosome Mapping; D019925:Cyclin A / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D005347:Fibroblasts / Q000502:physiology; D020869:Gene Expression Profiling; D005854:Germ Cells / Q000166:cytology*; D006066:Gonads / Q000166:cytology; D006652:Histological Techniques; D006657:Histones / Q000378:metabolism; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015336:Molecular Probe Techniques; D011233:Precipitin Tests; D013154:Spleen / Q000737:chemistry
D019925:Cyclin A; D019927:Cyclin E; D006657:Histones; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2