Phenotypic variation and targeted therapy of hypertrophic cardiomyopathy using genetic animal models

Michael P. Gannon, Mark S. Link

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


Hypertrophic cardiomyopathy (HCM) has a variable clinical presentation due to the diversity of causative genetic mutations. Animal models allow in vivo study of genotypic expression through non-invasive imaging, pathologic sampling, and force analysis. This review focuses on the spontaneous and induced mutations in various animal models affecting mainly sarcomere proteins. The sarcomere is comprised of thick (myosin) filaments and related proteins including myosin heavy chain and myosin binding protein-C; thin (actin) filament proteins and their associated regulators including tropomyosin, troponin I, troponin C, and troponin T. The regulatory milieu including transcription factors and cell signaling also play a significant role. Animal models provide a layered approach of understanding beginning with the causative mutation as a foundation. The functional consequences of protein energy utilization and calcium sensitivity in vivo and ex vivo can be studied. Beyond pathophysiologic disruption of sarcomere function, these models demonstrate the clinical sequalae of diastolic dysfunction, heart failure, and arrhythmogenic death. Through this cascade of understanding the mutation followed by their functional significance, targeted therapies have been developed and are briefly discussed.

Original languageEnglish (US)
Pages (from-to)20-31
Number of pages12
JournalTrends in Cardiovascular Medicine
Issue number1
StatePublished - Jan 2021


  • Animal models of human disease
  • Cardiomyopathy
  • Genetics
  • Hypertrophic cardiomyopathy
  • Sudden cardiac death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Phenotypic variation and targeted therapy of hypertrophic cardiomyopathy using genetic animal models'. Together they form a unique fingerprint.

Cite this