A premature-termination mutation in the Mus musculus cyclin-dependent kinase 3 gene

Our understanding of the mammalian cell cycle is due in large part to the a nalysis of cyclin-dependent kinase (CDK) 2 and CDK4/6. These kinases are re gulated by E and D type cyclins, respectively, and coordinate the G(1)/S-ph ase transition. In contrast, little is known about CDK3, a homolog of CDK2 and cell division cycle kinase 2 (CDC2). Previous studies using ectopic exp ression of human CDK3 suggest a role for this kinase in the G1/S-phase tran sition, but analysis of the endogenous kinase has been stymied by the low l evels of protein present in cells and by the absence of an identifiable cyc lin partner. Herein we report the presence of a single point mutation in th e CDK3 gene from several Mus musculus strains commonly used in the laborato ry. This mutation results in the replacement of a conserved tryptophan (Trp -187) within kinase consensus domain IX with a stop codon, The protein pred icted to be encoded by this allele is truncated near the T loop, which is i nvolved in activation by CDK-activating kinase. This mutation also deletes motif XI known to be required for kinase function and is, therefore, expect ed to generate a null allele. In stark contrast, CDK3 from two wild-mice sp ecies (Mus spretus and Mus mus castaneus) lack this mutation. These data in dicate that CDK3 is not required for M. musculus development and suggest th at any functional role played by CDK3 in the G(1)/S-phase transition is lik ely to be redundant with another CDK.