Loss of GATAD1 in cardiomyocyte does not cause cardiomyopathy in mice.

Abstract

GATA zinc finger domain containing 1 (GATAD1) is an as-yet uncharacterized zinc finger domain protein, which was initially identified as a histone 3 trimethylated at lysine 4 (H3K4me3) interactor. A recessive mutation in GATAD1 is associated with adult-onset dilated cardiomyopathy and heart failure, suggesting that GATAD1 is critical for maintaining normal cardiac structure and function. However, little is known as to the specific role of GATAD1 in cardiomyocytes. A mammalian Gatad1 knockout model has yet to be generated for investigating its specific role in the heart. To address this, we generated a Gatad1 cardiomyocyte-specific knockout (cKO) mouse model. Gatad1 cKO mutants exhibited normal cardiac function during the aging process up to 18 months of age. Unlike the abnormal nuclei shape observed in patients carrying GATAD1 mutations, the nuclei shape of cardiomyocytes remained unaffected by the loss of Gatad1. Furthermore, Gatad1 cKO mice responded normally to pressure overload induced by transverse aortic constriction (TAC) surgery. Together, these observations suggest that deletion of Gatad1 in cardiomyocytes does not induce cardiomyopathy during aging or affect the response to pressure overload stress in mice.