Cdkn2b Conditional Knockout mouse models

Cdkn2b, mouse ortholog of human CDKN2B, encodes p15INK4b, an ankyrin repeat INK4 family inhibitor that binds CDK4 and CDK6 monomers and prevents productive D-cyclin association, thereby holding RB hypophosphorylated. Unlike p16, p15 is strongly transcriptionally induced by TGF beta through SMAD3 and SMAD4 with FOXO cofactors, making it the principal effector of cytostatic TGF beta signaling in epithelial and hematopoietic cells, and it is also silenced by promoter hypermethylation in acute myeloid leukemia and myelodysplastic syndrome. Because CDKN2B sits immediately adjacent to CDKN2A within the 9p21 cluster, most human deletions remove both, so a mouse allele targeting p15 alone is the only way to assign phenotype to this gene. Null mice are viable and develop lymphoid hyperplasia and angiosarcoma at low penetrance, and p16 upregulation genuinely compensates for p15 loss, so compound Cdkn2a and Cdkn2b alleles are required for the human co-deletion state. Use isolated nulls for TGF beta cytostasis and compound deletions for 9p21 tumor modeling.

Cdkn2b conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.