Animal models of hypertrophic cardiomyopathy

Familial hypertrophic cardiomyopathy (FHC) is an autosomal-dominant disease that is both clinically and genetically heterogeneous. Disease-causing mut ations have been found in eight genes encoding structural components of the thick and thin filament systems of the cardiac myocyte; it has therefore b een coined a disease of the sarcomere, How each mutation leads to the diver se clinical phenotypes is still obscure, and research in this area is Very active. Many approaches have been used to characterize the pathogenesis of the disease. Biochemical characterization of mutant alleles expressed in vi tro has shed some insight into the functional deficits of several mutant al leles of myosin heavy chain, troponin-T, and alpha-tropomyosin. Transgenic animal models for FHC have been created to gain further insight into the pa thogenesis of this disease. Most of these models have been made in mice; ho wever, recently a transgenic rabbit model has been created. In addition, th ere are several natural-occurring forms of FHC in animals that will be inte resting to explore. The discovery of additional responsible genes and the e lucidation of the molecular mechanisms of pathogenesis through the use of a nimal models promise improved and early diagnosis and the potential for dev eloping specific, mutation-, or mechanism-based therapeutics. (C) 2000 Lipp incott Williams & Wilkins, Inc.