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TAC Induced Hypertrophic Cardiomyopathy Model

Hypertrophic Cardiomyopathy (HCM) is a type of cardiomyopathy characterized by thickening of the left ventricular wall, asymmetric septal hypertrophy, reduced left ventricular cavity size, and preserved or enhanced left ventricular ejection fraction. The transverse aortic constriction (TAC) model is a relatively classic surgical model of hypertrophic cardiomyopathy. It can simulate myocardial hypertrophy due to increased cardiac afterload and the subsequent transition to chronic heart failure, similar to human conditions such as hypertension or aortic valve stenosis-induced heart failure.

GemPharmatech has developed a TAC model by ligating the transverse aorta of C57BL/6JGpt mice. In this model, mice develop hypertrophic cardiomyopathy four weeks after surgery and progress to heart failure by eight weeks. This model can be used for research on hypertrophic cardiomyopathy, the mechanisms of heart failure, and the evaluation of related small-molecule drugs.

1.After 4 and 8 weeks of TAC modeling, the mouse hearts showed significant enlargement, with a noticeable increase in the heart weight-to-body weight ratio(HW/BW) and the heart weight-to-tibia length ratio (HW/TL), consistent with a hypertrophic myocardial phenotype.

2.After 4 weeks of TAC modeling, the mouse hearts exhibited a significant reduction in systolic function (reduced EF and FS). There was also a noticeable increase in the thickness of the left ventricular wall (LVPW, LVAW, IVS), and significant enlargement in left ventricular systolic diameter and internal diameter (Diameter;s, LVID;s, Volume;s), as well as a significant increase in left ventricular mass (LV mass), consistent with a hypertrophic myocardial phenotype.

3.The results of the ex vivo examination of the mouse hearts after 4 weeks of TAC modeling show a significant increase in cardiac volume, thickening of the ventricular walls, and mild myocardial fibrosis.

In addition to the TAC-induced model, GemPharmatech has also developed genetically engineered models of hypertrophic cardiomyopathy. Myh6 R404Q mice exhibit a phenotype characterized by myocardial hypertrophy and enhanced cardiac contractility, while Mybpc3 KO mice display ventricular dilation, thickening of the ventricular walls, and a phenotype associated with congenital heart failure. Both of these mouse models can serve as models for hypertrophic cardiomyopathy, but due to their distinct phenotypes, they may have different applications, contributing to the exploration of hypertrophic cardiomyopathy mechanisms and drug development.

Strain Number Strain Name Strain Type Applications
T051403 Myh6 R404Q Point mutation 1. Anti-familial hypertrophic cardiomyopathy (FHC) drug screening and efficacy test;

2. Research on related diseases (such as myocardial hypertrophy and fibrosis) caused

by defects of Myh6 (R404Q point mutation).

T027708 Mybpc3 KO Knock-out 1. Anti-HCM or dilated cardiomyopathy (DCM)drug screening and efficacy test.

2. Research on related diseases (such as myocardial hypertrophy, ventricular dilation and fibrosis) caused by defects of Mybpc3.

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