Cdk2 Conditional Knockout mouse — CD4-Cre pairing

Cdk2, the mouse ortholog of human CDK2, encodes the cyclin dependent kinase that partners cyclin E in late G1 and cyclin A in S phase, requiring CAK phosphorylation of threonine 160 in the activation loop and inhibition by p21 and p27, and phosphorylating RB, p27 itself, CDC6, NPAT and nucleophosmin to coordinate origin licensing, histone synthesis and centrosome duplication. Loss of function is surprisingly tolerated because CDK1 binds cyclin E and cyclin A and executes S phase entry, so null mice are viable and only sterile from meiotic prophase failure at the telomere attachment step, a phenotype that makes this a clean reproductive biology model. That redundancy sets the design logic: conditional nulls are best for germ cell and CCNE1 amplified synthetic lethality studies, whereas analog-sensitive gatekeeper knockins allow acute chemical genetic inhibition that outperforms genetic deletion. Combine with Ccne1 or Ccne2 alleles when the endpoint is replication stress rather than proliferation, and pair with a germline or tumor-restricted Cre.

Conditional deletion of Cdk2 limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Cdk2 floxed stock yields usable cohorts. For T cell work, plan Cre specificity, reporter crosses, and baseline phenotyping before you scale.