Similarly, genetic variations in ISL1 have been associated with susceptibility to ventricular septal defect43 and non-syndromic, complex congenital heart disease17 in human patients, whereas ISL1 haploinsufficiency is associated with d-transposition of the great arteries.16 Thus, our Isl1 hypomorphic mouse model represents a valuable genetic system to gain new insights into the etiology of congenital heart defects and for developing novel therapeutic strategies. This evidence concerns the gene ISL1 and congenital heart disease.