The obtained caAcvr1:Nfatc1 mutants that were homozygous for Enpp1 (Enpp1−/−) died in utero, and thus could not be used to study the progression of aortic valve disease, while caAcvr2:Nfatc1:Enppi+/− mice were phenotypically indistinguishable from their caAcvr1:Nfatc1Cre littermates. Here, NFATC1 is linked to aortic valve disorder.