Applications of Genetically Engineered Mouse Models for Hypertrophic Cardiomyopathy Research

Hypertrophic cardiomyopathy (HCM) is a prevalent and genetically heterogeneous cardiovascular disorder, with approximately 55% of familial cases linked to mutations in sarcomeric genes. To enable mechanistic and therapeutic studies, GemPharmatech has successfully developed two HCM mouse models: the Mybpc3 knockout (KO) and the Myh6 R404Q (point mutation) strains.

MYBPC3 encodes cardiac myosin-binding protein C (cMyBP-C), a thick filament-associated protein that regulates myocardial contraction and relaxation by modulating actin-myosin cross-bridge interactions, acting as a molecular brake to limit excessive cross-bridge cycling. The Mybpc3 KO model recapitulates human MYBPC3-related cardiomyopathy, exhibiting eccentric hypertrophy with associated systolic dysfunction, accelerated myosin cycling kinetics, and increased arrhythmia susceptibility. This strain is particularly suitable for anti-HCM drug screening and gene therapy efficacy testing aimed at restoring human MYBPC3 expression in cardiomyocytes.

In mice, Myh6 encodes alpha-myosin heavy chain (α-MHC), which shares functional homology with human MYH7. The R404Q point mutation in murine Myh6 corresponds topologically and structurally to the human MYH7 R403Q pathogenic variant, disrupting the binding affinity between myosin heavy chain and cMyBP-C. The Myh6 R404Q model recapitulates a concentric hypertrophy phenotype, characterized by preserved or enhanced systolic function and mild-to-moderate diastolic dysfunction, as confirmed by echocardiography and pressure-volume (PV) loop analysis. This model is well-suited for efficacy testing of anti-familial HCM (FHC) therapeutics and for investigating mutation-specific pathologies, including cardiomyocyte hypertrophy and interstitial fibrosis.

In this webinar, our scientist will walk you through current state of HCM research, the two advanced HCM mouse models, efficacy testing case studies, and GemPharmatech's comprehensive platform for precise cardiac function assessment.

Topics for this webinar include:

• Introduction of HCM-associated gene mutations

• Overview of Mybpc3 KO and Myh6 R404Q phenotypes

• Case studies utilizing HCM mouse models

• Demonstration of cardiac function assessment tools, including echocardiography and PV loop catheterization