Interestingly, while mice which are homozygous for a null mutation in endothelial NOS (Nos3−/−) display a partially penetrant BAV at an incidence of ∼25% (117, 118), Notch1; Nos3 compound mutant mice (Notch1+/−; Nos3−/−) display congenital aortic valve disease such as BAV and AVS at a penetrance of 64%. The gene discussed is NOS3; the disease is aortic valve disorder.