Ortega Sagrario, Prieto Ignacio, Odajima Junko, Martín Alberto, Dubus Pierre, Sotillo Rocio, Barbero Jose Luis, Malumbres Marcos, Barbacid Mariano
Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, Madrid E-28029, Spain.
Nat Genet. 2003 Sep;35(1):25-31. doi: 10.1038/ng1232. Epub 2003 Aug 17.
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.
我们通过同源重组在小鼠胚胎干细胞(ES细胞)中靶向编码细胞周期蛋白依赖性激酶2(CDK2)的基因座。缺乏CDK2的胚胎成纤维细胞正常增殖,并在培养中连续传代后变得永生化。在永生化细胞中消除条件性Cdk2等位基因对增殖没有显著影响。Cdk2基因敲除小鼠是可行的,可存活长达两年,这表明CDK2对于大多数细胞类型的增殖和存活也是可有可无的。但是CDK2对于雄性和雌性生殖细胞减数分裂前期I的完成至关重要,这是这种细胞周期激酶未曾预料到的作用。