Sarcomeric Thin Filament Associated Cardiomyopathic Mouse Models

Abstract

Cardiomyopathies are diseases primarily associated with defects in the structure and physiological function of the heart. Hypertrophic and dilated cardiomyopathies are two common conditions associated with severe pathological abnormalities that often lead to heart failure. Studies in the early 1990’s by the Seidman laboratories linked hypertrophic cardiomyopathy with mutations in both thick and thin sarcomeric protein genes. Since then, the development and analysis of animal models of both hypertrophic and dilated cardiomyopathy has significantly advanced our knowledge of the structural, molecular, biochemical, and physiological disease processes that lead to these cardiomyopathic conditions. The focus of this article is an examination of mouse models of hypertrophic and dilated cardiomyopathies with mutations in sarcomeric thin filament protein genes (actin, tropomyosin, troponin T, I, and C) and the information these models provide in our understanding of the disease processes. Special attention addresses the significant role that tropomyosin mutation models have contributed to this information. In addition, we address how various methods have been developed to phenotypically rescue these diseased hearts with respect to their morphological and physiological functions. By thorough analysis of these mouse models, not only can we better understand the disease processes, but there is a great potential for the development of effective therapeutics to treat these severe pathological conditions.