Age-related changes in familial hypertrophic cardiomyopathy phenotype in transgenic mice and humans

Hong chang Luo, Iraklis Pozios, Styliani Vakrou, Lars Sorensen, Roselle M. Abraham, Theodore Abraham

Research output: Contribution to journalArticlepeer-review


β-myosin heavy chain mutations are the most frequently identified basis for hypertrophic cardiomyopathy (HCM). A transgenic mouse model (αMHC403) has been extensively used to study various mechanistic aspects of HCM. There is general skepticism whether mouse and human disease features are similar. Herein we compare morphologic and functional characteristics, and disease evolution, in a transgenic mouse and a single family with a MHC mutation. Ten male αMHC403 transgenic mice (at t-5 weeks, −12 weeks, and −24 weeks) and 10 HCM patients from the same family with a β-myosin heavy chain mutation were enrolled. Morphometric, conventional echocardiographic, tissue Doppler and strain analytic characteristics of transgenic mice and HCM patients were assessed. Ten male transgenic mice (αMHC403) were examined at ages −5 weeks, −12 weeks, and −24 weeks. In the transgenic mice, aging was associated with a significant increase in septal (0.59±0.06 vs. 0.64±0.05 vs. 0.69±0.11 mm, P<0.01) and anterior wall thickness (0.58±0.1 vs. 0.62±0.07 vs. 0.80±0.16 mm, P<0.001), which was coincident with a significant decrease in circumferential strain (−22%±4% vs. −20%±3% vs. −19%±3%, P=0.03), global longitudinal strain (−19%±3% vs. −17%±2% vs. −16%±3%, P=0.001) and E/A ratio (1.9±0.3 vs. 1.7±0.3 vs. 1.4±0.3, P=0.01). The HCM patients were classified into 1st generation (n=6; mean age 53±6 years), and 2nd generation (n=4; mean age 32±8 years). Septal thickness (2.2±0.9 vs. 1.4±0.1 cm, P<0.05), left atrial (LA) volume (62±16 vs. 41±5 mL, P=0.03), E/A ratio (0.77±0.21 vs. 1.1±0.1, P=0.01), E/e’ ratio (25±10 vs. 12±2, P=0.03), global left ventricular (LV) strain (−14%±3% vs. −20%±3%, P=0.01) and global LV early diastolic strain rate (0.76±0.17 s−1vs. 1.3±0.2 s-1, P=0.01) were significantly worse in the older generation. In β-myosin heavy chain mutations, transgenic mice and humans have similar progression in morphologic and functional abnormalities. The αMHC403 transgenic mouse model closely recapitulates human disease.

Original languageEnglish (US)
Pages (from-to)634-639
Number of pages6
JournalJournal of Huazhong University of Science and Technology - Medical Science
Issue number5
StatePublished - Oct 16 2014


  • age-related
  • familial hypertrophic cardiomyopathy
  • transgenic mice

ASJC Scopus subject areas

  • Biochemistry
  • Biomaterials
  • Biomedical Engineering
  • Genetics


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