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Updated: Aug 11, 2026
Transverse Aortic Constriction in Mice
Published on: April 21, 2010
Gender and aging in a transgenic mouse model of hypertrophic cardiomyopathy
M C Olsson1, B M Palmer, L A Leinwand
1Department of Kinesiology and Applied Physiology, University of Colorado, Boulder 80309-0354, USA.
Insights
Familial hypertrophic cardiomyopathy (FHC) is linked to cardiac myosin mutations. This study shows a transgenic mouse model develops FHC-like changes, with differing impacts on male and female heart function over time.
Area of Science:
- Cardiovascular Biology
- Genetics
- Translational Medicine
Background:
- Mutations in cardiac myosin heavy chain (MHC) are a primary cause of familial hypertrophic cardiomyopathy (FHC).
- Understanding FHC pathogenesis requires robust animal models that recapitulate human disease phenotypes.
Purpose of the Study:
- To characterize the cardiac contractile function and structural changes in a novel transgenic mouse model expressing mutant alpha-MHC.
- To investigate the sex-specific progression of cardiac dysfunction in this FHC model.
Main Methods:
- Development of a transgenic mouse model expressing R403Q and actin-binding deletion mutations in alpha-MHC.
- Utilized an isovolumic left heart preparation to assess cardiac contractility in transgenic (TG) and wild-type (WT) mice.
- Evaluated cardiac structure and function at 4 and 10 months of age in both male and female mice.
Main Results:
- Transgenic mice developed left ventricular (LV) hypertrophy and diastolic dysfunction by 4 months.
- At 10 months, female TG mice showed persistent hypertrophy and diastolic dysfunction, while males exhibited LV dilation and impaired systolic function.
- Both sexes displayed diminished coronary flow at 10 months, indicating compromised cardiac energetics.
Conclusions:
- This transgenic mouse model effectively mimics key pathological features of human FHC, including sex-specific disease progression.
- The observed cardiac remodeling and functional decline highlight the utility of this model for studying FHC pathogenesis and testing therapeutic strategies.
Abstract:
Mutations in the cardiac myosin heavy chain (MHC) can cause familial hypertrophic cardiomyopathy (FHC). A transgenic mouse model has been developed in which a missense (R403Q) allele and an actin-binding deletion in the alpha-MHC are expressed in the heart. We used an isovolumic left heart preparation to study the contractile characteristics of hearts from transgenic (TG) mice and their wild-type (WT) littermates. Both male and female TG mice developed left ventricular (LV) hypertrophy at 4 mo of age. LV hypertrophy was accompanied by LV diastolic dysfunction, but LV systolic function was normal and supranormal in the young TG females and males, respectively. At 10 mo of age, the females continued to present with LV concentric hypertrophy, whereas the males began to display LV dilation. In female TG mice at 10 mo of age, impaired LV diastolic function persisted without evidence of systolic dysfunction. In contrast, in 10-mo-old male TG mice, LV diastolic function worsened and systolic performance was impaired. Diminished coronary flow was observed in both 10-mo-old TG groups. These types of changes may contribute to the functional decompensation typically seen in hypertrophic cardiomyopathy. Collectively, these results further underscore the potential utility of this transgenic mouse model in elucidating pathogenesis of FHC.
