Cardiac electrophysiology in genetically engineered mice.

The mouse has become the principal animal model for studying biologic processes in mammals. Major advances in transgene and gene targeting technology enabled manipulation of the mouse genome in a predictable fashion. Mutant mouse strains provide important insights into the molecular mechanisms underlying normal and disordered cardiac conduction and sudden cardiac death. A variety of mouse strains harboring gene mutations leading to inherited developmental disorders have been designed. Structural protein abnormalities, connexin protein defects, and ion channelopathies associated with human clinical phenotypes, including congenital heart disease, cardiomyopathies, long QT syndrome, and muscular dystrophy, have been engineered into the mouse genome, creating models of human electrophysiologic disease. Functional analyses of the underlying molecular mechanisms of resultant phenotypes require appropriate and sophisticated experimental methodology. In this review, genetic mouse models pertinent to human arrhythmogenic disorders and their application to present-day ex vivo and in vivo murine electrophysiologic technology at the whole organ and animal levels are discussed.