To determine whether the deficiency in ACTH response involved PKA holoenzyme or occurred upstream of the kinase, we assessed the capacity of genetic activation of PKA to rescue adrenal insufficiency in Senp2cKO mice by removing the RIα subunit (Prkar1a floxed allele) known to repress PKA catalytic activity7,9,28. The gene discussed is PRKAR1A; the disease is Adrenal insufficiency.