Cyp26a1 Conditional Knockout mouse models

Cyp26a1, ortholog of human CYP26A1, encodes the principal retinoic acid catabolizing cytochrome P450, a microsomal enzyme that hydroxylates all-trans retinoic acid at carbon 4 and drives it toward oxo and polar metabolites, thereby carving retinoid-free zones adjacent to RALDH2-derived source domains and sharpening hindbrain, tailbud, and limb boundaries. The gene is itself a direct RAR target, forming a negative feedback loop that buffers retinoid excess, and its induction contributes to resistance against all-trans retinoic acid therapy in acute promyelocytic leukemia. Germline nulls die during gestation or shortly after birth with caudal truncation, spina bifida, and cervical vertebral transformations that phenocopy retinoid teratogenesis, so any postnatal or adult study requires conditional floxed alleles. Enzyme-dead knockins distinguish catalysis from expression, and humanized alleles are appropriate for testing CYP26 inhibitors such as talarozole. Because Cyp26b1 and Cyp26c1 clear retinoic acid in adjacent territories, compound conditionals are needed where domains abut, notably hindbrain rhombomeres.

Conditional deletion of Cyp26a1 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 Cyp26a1 floxed stock yields usable cohorts.