Prkaa1 Conditional Knockout mouse models

Prkaa1 encodes AMPK alpha1, one of two catalytic subunits orthologous to human PRKAA1, comprising an amino-terminal kinase domain, an autoinhibitory sequence and a carboxy-terminal region that tethers the beta and gamma subunits. Activation requires Thr172 phosphorylation by LKB1 or, upon calcium flux, by CaMKK2, and is sustained allosterically when adenine nucleotide occupancy of the gamma subunit protects that site from phosphatases; downstream, the kinase phosphorylates ACC1 Ser79, TSC2, RAPTOR Ser792 and ULK1 to suppress anabolism and license autophagy. Alpha1 predominates in most tissues except skeletal muscle and liver, where alpha2 dominates, so single deletion often yields a partial phenotype and compound Prkaa1 and Prkaa2 alleles are usually necessary; combined deletion is embryonically lethal, making conditional pairs the practical route. Thr172 phospho-dead knockins separate upstream kinase input from intrinsic catalysis, which matters when interpreting metformin and direct activator studies.

Prkaa1 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.