ABSTRACT
INTRODUCTION Congenital heart disease currently affects one in 200 births in the United States annually. Each case is composed o f a constellation of well-defined defects such as abnormalities in septation, valvular formation, vascular development, car diac chamber growth, and right-to-left positional orientation of the heart or great vessels. These phenotypical changes are easily identified, yet few associated candidate genes or molecular insights have been recognized. Although our current understanding of cardiovascular developmental defects is itself at an embryonic stage, this area is likely to be one o f the major beneficiaries o f advances in mouse genetics through the generation o f trans genic and gene-targeted animal model systems. Recent contributions to our understanding o f the developmental regulation o f genetic markers o f cardiac chamber formation and specification, combined with studies on the molecular switches that regulate the expression o f these markers, are beginning to provide a foundation from which to analyze the complex process o f car diogenesis. In addition, the development o f microsurgical approaches, minia turized catheterization techniques, microangiography, and high-speed video microscopy has allowed the quantitative analysis o f complex physiological phenotypes in vivo, in genetically manipulated adult mice and recently in the murine embryo. Further, a number o f laboratories have identified chromo somal markers that are closely linked with genetic cardiovascular develop mental defects in humans, including Holt-Oram syndrome, supravalvular
aortic stenosis, and the “Catch-22 syndromes” (conotruncal anomaly face, Shprintzen’s syndrome, and DiGeorge’s syndrome).
