Mouse Models of Congenital Heart Defects

Abstract

One of the puzzling things about genetic disruptions in mice that affect heart development is the overwhelming number of conotruncal anomalies and the infrequency with which certain other malformations are reported. For instance, venous malformations such as total anomalous pulmonary venous return (TAPVR) or partial anomalous pulmonary venous return (PAPVR) have not been reported in a mutant mouse. Coronary artery anomalies are reported infrequently, and when they are reported it is because they are obvious. Conotruncal anomalies such as common trunk, double-outlet right ventricle, and pulmonary stenosis with overriding aorta are frequently associated with mouse germ line and conditional gene deletions. Although conotruncal malformations represent the highest percentage of congenital heart defects in the human population, TAPVR and PAPVR occur in a significant number of babies. Further, coronary anomalies affecting the stems of the coronary arteries frequently are seen in conotruncal malformations in babies but are rarely reported in mouse models. Article see p 314 Isolated TAPVR is a rare lesion and occurs in only about 1 in 17 000 live births.1 PAPVR is much more common and has been reported in 1 in 160 individuals (0.6%) and 0.4% to 0.7% of postmortem examinations, with 90% of these associated with an atrial septal defect.2 The majority of patients with TAPVR have symptoms of cyanosis and congestion within the first year of life. If left untreated, about 80% would die. In contrast, PAPVR frequently is not discovered until adulthood and is not usually a cause of death. Although the overall incidence of PAPVR in autopsy cases has been estimated to be 0.7%,3 the true prevalence may be higher,4 as several reports have appeared with PAPVR as an incidental finding that in most of these cases is asymptomatic. PAPVR can present as an isolated structural abnormality, but it …