Knocking out Pde1a induced mild renal cystic disease and a urine concentrating defect (associated with upregulation of PDE4 activity and a decrease in protein kinase A dependent phosphorylation of aquaporin-2) on a wild-type genetic background and aggravated the renal cystic disease on a Pkd2WS25/- background. The gene discussed is AQP2; the disease is cystic kidney disease.