Animal models of hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy (FHC) is an autosomal-dominant disease that is both clinically and genetically heterogeneous. Disease-causing mutations have been found in eight genes encoding structural components of the thick and thin filament systems of the cardiac myocyte; it has therefore been coined a disease of the sarcomere. How each mutation leads to the diverse 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 vitro has shed some insight into the functional deficits of several mutant alleles of myosin heavy chain, troponin-T, and alpha-tropomyosin. Transgenic animal models for FHC have been created to gain further insight into the pathogenesis of this disease. Most of these models have been made in mice; however, recently a transgenic rabbit model has been created. In addition, there are several natural-occurring forms of FHC in animals that will be interesting to explore. The discovery of additional responsible genes and the elucidation of the molecular mechanisms of pathogenesis through the use of animal models promise improved and early diagnosis and the potential for developing specific, mutation-, or mechanism-based therapeutics.