Using tissue-specific gene knockout technology in mice, we have generated mouse lines deficient in endocardial transcription factors or chromatin remodeling molecules. One of the mutant lines develops abnormal myocardial growth and trabeculation. These observations suggest that endocardial factors are required for myocardial development. We are studying the molecular and cellular mechanisms of how endocardial cells control myocardial development. Furthermore, we have generated several mouse lines lacking myocardial or epicardial transcription factors or chromatin remodeling molecules. These mice fail to form mature myocardium, interventricular septum or coronary arteries. We are investigating the molecular basis of these cardiac and vascular defects.