Hypertrophic Cardiomyopathy Animal Model Service

Hypertrophic cardiomyopathy animal model service provides a comprehensive and customizable platform for in vivo efficacy and mechanistic studies. Protheragen specializes in developing and validating highly translatable animal models that accurately recapitulate the genetic, molecular, and pathophysiological hallmarks of human hypertrophic cardiomyopathy, offering end-to-end support from model selection and creation to detailed phenotypic characterization and preclinical drug evaluation.

Introduction to Hypertrophic Cardiomyopathy Animal Models

Hypertrophic cardiomyopathy, the most common inherited cardiac condition, is caused by mutations within the sarcomeric proteins, resulting in left ventricular hypertrophy, myofiber disarray, interstitial fibrosis, and an increased likelihood of arrhythmias and sudden cardiac death. Reliable animal models are fundamental for understanding the complex mechanisms of the disease and developing therapeutics. Such models are vital for assessing the effectiveness of new drugs, testing gene therapy, and evaluating other therapies, bridging the gap between basic research and application.

Fig.1 Administration scheme of plicamycin or ML264 in hypertrophic cardiomyopathy mice. (Gao, J., et al., 2024)

Our Services

Leveraging our deep expertise in cardiovascular pathophysiology and sophisticated in vivo model generation, we provide a robust, one-stop service for hypertrophic cardiomyopathy research and drug development. Our core strengths lie in the meticulous design and validation of highly translatable animal models, which enable us to deliver highly reliable and reproducible data, accelerating your drug discovery pipeline from initial target validation through to application studies with a high level of scientific rigor.

Animal Models of Hypertrophic Cardiomyopathy

Genetically Engineered Models

Offering expert development of genetically engineered animal models for hypertrophic cardiomyopathy, we provide a powerful and precise solution for target discovery and therapeutic validation. From initial model design to comprehensive genotyping and phenotypic characterization, the animal model services are tailored to specific research requirements.

Optional models:

• Myh6 mutation model
• Mybpc3 knockout model
• Tnnt2 mutation model

• Tpm1 mutation model
• Tnni3 mutation model
• Others

Mouse Model for Hypertrophic Cardiomyopathy Research

Case Study-Myh6^R404Q/+ Hypertrophic Cardiomyopathy Mouse Model Development

Model Introduction

Carrying a well-characterized human pathogenic mutation in a critical sarcomeric gene, the Myh6^R404Q/+ mouse model provides a highly faithful in vivo system that recapitulates the hallmark structural and functional progression of human hypertrophic cardiomyopathy. This model enables comprehensive profiling of the efficacy and safety of novel therapeutic candidates.

Methodology

• Animal Model: A targeted point mutation was introduced into the Myh6 gene on a C57BL/6J background using advanced gene-editing technology. This engineering strategy specifically altered exon 13 to generate the Myh6-R404Q point mutation, replicating a known human pathogenic variant associated with hypertrophic cardiomyopathy.
• Phenotypic Analysis Methods: Cardiac phenotyping was performed using non-invasive transthoracic echocardiography. High-resolution imaging was conducted at predetermined intervals throughout the study, yielding comprehensive echocardiographic data. Assessed parameters included functional indices such as ejection fraction (EF) and fractional shortening (FS), in addition to structural measurements of left ventricular mass, wall thickness, and internal dimensions.

Phenotypic Analysis & Results

Echocardiographic assessment revealed a progressive hypertrophic phenotype in heterozygous mutants relative to wild-type (WT) controls. Significant increases in left ventricular posterior wall thickness were observed as early as 8 weeks of age, followed by elevated EF and FS by 16 weeks. With advancing age, further pathological remodeling was documented, characterized by significantly reduced left ventricular internal dimensions (LVID) and chamber volumes (LVEDV, LVESV). This was accompanied by a decrease in cardiac output, consistent with a concentric hypertrophic cardiomyopathy phenotype.

Fig.2 Cardiac phenotype in Myh6^R404Q/+ hypertrophic cardiomyopathy model. Echocardiographic analysis of heterozygous Myh6^R404Q/+ and WT mice. Myh6^R404Q/+ hearts exhibited marked reductions in LVID, end-diastolic volume (LVEDV), and end-systolic volume (LVESV), along with increases in EF and FS. Data are presented as mean ± SEM (n=5; ***p < 0.0001, **p < 0.01).

Conclusion

Collectively, these data demonstrate that this genetically engineered model successfully recapitulates the pathophysiological trajectory of human hypertrophic cardiomyopathy, from early concentric hypertrophy to eventual functional decline. Characterized by high pathological fidelity and reproducibility, the model offers an indispensable and predictive platform for investigating disease mechanisms and conducting rigorous preclinical evaluation of potential therapeutics, thereby accelerating the drug development pipeline for this complex cardiovascular disorder.

Contact Us

Beyond animal model provision, Protheragen's integrated service suite ensures a complete preclinical assessment of your candidate therapeutic. We conduct rigorous pharmacokinetics studies to elucidate absorption, distribution, metabolism, and excretion profiles, alongside detailed pharmacodynamics assessments. Furthermore, our capabilities extend to full drug safety and toxicology evaluations, including histopathological analysis and biomarker assessment, to de-risk your program and provide the data package required. Contact us to discuss how our hypertrophic cardiomyopathy animal model service can be tailored to advance your specific research and drug development goals.

Reference

• Gao, Junpeng et al. "Integrative analysis of transcriptome, DNA methylome, and chromatin accessibility reveals candidate therapeutic targets in hypertrophic cardiomyopathy." Protein & cell 15.11 (2024): 796-817.