CARDIAC PHYSIOLOGY IN TRANSGENIC MICE

By use of gene targeting and/or transgenesis, it is now possible to ma ke defined changes in genes whose functions underlie mammalian cardiov ascular function. Because of technical and economic considerations, th ese experiments are largely confined to the mouse. Genetic modificatio n of the loci responsible for aspects of cardiac development, differen tiation, and function via gene targeting, as well as modulation of the cardiac protein complement using transgenesis, has begun to provide m ouse models of cardiac hypertrophy, dilated cardiomyopathy, and hypert rophic cardiomyopathies. In order to use these animal models fully and explore their phenotypes at the whole organ and whole animal levels, the extension of cardiovascular physiological methodologies to the mou se is imperative. Techniques for exploring aspects of cardiovascular f unction are well developed for larger animal models, but their modific ation for the small size of the mouse heart and for the animal's rapid cardiac cycle has proven to be a formidable challenge, requiring the combined efforts of the molecular biology, physiology, and cardiology communities. We review here the ability of present-day technology to o btain reproducible data on murine cardiac function at the whole organ and animal levels.