Given the recent reports of genetic involvement of TGFB3 mutations in the cardiovascular disease in humans [6,7,9,12], our paradigm-shifting findings demonstrate that the majority of Tgfb3−/− fetuses develop both cardiac outflow tract (OFT) and atrioventricular (AV) canal defects and that the loss of Tgfb3 leads to major myocardial defects, particularly affecting the right ventricular myocardium. This evidence concerns the gene TGFB3 and cardiovascular disorder.