TRANSGENIC ANIMAL-MODELS - NEW AVENUES IN CARDIOVASCULAR PHYSIOLOGY

Application of molecular genetic tools to inherited cardiovascular dis orders has provided important insights into the molecular mechanisms u nderlying cardiomyopathies, arrhythmias, blood pressure regulation, an d atherosclerosis. In addition, alteration of gene expression has been observed under common cardiovascular conditions such as cardiac hyper trophy and heart failure. Recent advances in transgenic and gene-targe ting approaches allow a sophisticated manipulation of the mouse genome by gene addition, gene deletion, or gene modifications. These transge nic models enable the dissection of in vivo pathways responsible for t hese complex disease phenotypes. This review describes tissue-specific promoters suitable for targeting candidate genes to the cardiovascula r system as well as a number of valuable transgenic animal models of b lood pressure regulation, atherogenesis, defects in the coagulation sy stem, cardiac hypertrophy, myocarditis, cardiomyopathies, and heart fa ilure. Limitations and difficulties associated with these transgenic a pproaches are discussed. Animal models which may provide a basis for f uture gene therapy of cardiovascular diseases are introduced. Finally, methods are described to regulate the spatial and temporal expression level of a transgene, to inactivate a target gene in a tissue-specifi c manner, and to introduce specific mutations into the genome. These r ecent advances in transgenic technology are expected to have a conside rable impact on cardiovascular research in the near future.