CARDIAC-MUSCLE DISEASES IN GENETICALLY-ENGINEERED MICE - EVOLUTION OFMOLECULAR PHYSIOLOGY

Recent advances in molecular, cellular, and genetically based technolo gies now offer the possibility of generating genetically engineered mi ce that display physiological phenotypes with direct relevance to huma n pathophysiological states. The ability to create gene ablations, gen e duplications, and gene modifications should allow the use of genetic approaches to map in vivo pathways responsible for complex physiologi cal phenotypes. Recent work from our laboratory utilizing this approac h to study cardiac muscle diseases in both the adult context (cardiac hypertrophy) and in the embryonic context (congenital ventricular defe cts) will be discussed, as well as the steps that led to the generatio n and characterization of these novel mouse model systems. A large bod y of work from independent laboratories now points to the inception of a new field of molecular physiology that will fuse mouse genetics and in vivo physiology using appropriate miniaturized physiological techn ology. Recent advances and prospects for future directions are summari zed.