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Updated: Jun 23, 2026
Modeling Myotonic Dystrophy 1 in C2C12 Myoblast Cells
Published on: July 29, 2016
A mouse model of myosin binding protein C human familial hypertrophic cardiomyopathy
1Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
Insights
Mutant myosin binding protein C (MyBP-C) expression in mice hearts disrupts sarcomere structure and reduces muscle power. This study reveals how truncated MyBP-C impacts cardiac function and protein regulation.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Genetics
Background:
- Familial hypertrophic cardiomyopathy (HCM) is linked to mutations in sarcomeric proteins.
- Cardiac myosin binding protein C (MyBP-C) mutations, particularly those causing truncated forms, are associated with HCM.
- Understanding the functional consequences of MyBP-C mutations is crucial for HCM research.
Purpose of the Study:
- To investigate the effects of expressing a mutated, truncated MyBP-C in the heart using a transgenic mouse model.
- To determine how this mutant MyBP-C affects sarcomere structure, function, and endogenous MyBP-C levels.
Main Methods:
- Creation of transgenic mice expressing a mutated MyBP-C lacking myosin and titin binding domains.
- Analysis of the stability and sarcomeric incorporation of the transgenically encoded truncated protein.
- Assessment of muscle fiber contractility using pCa2+-force curves and measurement of power output.
- Evaluation of endogenous MyBP-C levels and sarcomere organization in transgenic hearts.
Main Results:
- The truncated MyBP-C protein was stable but not efficiently incorporated into the sarcomere.
- Transgenic muscle fibers exhibited a leftward shift in the pCa2+-force curve, indicating altered calcium sensitivity.
- Muscle power output was significantly reduced in transgenic mice.
- Expression of mutant MyBP-C led to decreased endogenous MyBP-C levels and striking sarcomere disorganization and dysgenesis.
Conclusions:
- Truncated MyBP-C expression disrupts normal sarcomere structure and function.
- Mutant MyBP-C expression interferes with endogenous MyBP-C levels, exacerbating cardiac pathology.
- This model provides insights into the pathogenesis of HCM caused by MyBP-C mutations.
Abstract:
Familial hypertrophic cardiomyopathy can be caused by mutations in genes encoding sarcomeric proteins, including the cardiac isoform of myosin binding protein C (MyBP-C), and multiple mutations which cause truncated forms of the protein to be made are linked to the disease. We have created transgenic mice in which varying amounts of a mutated MyBP-C, lacking the myosin and titin binding domains, are expressed in the heart. The transgenically encoded, truncated protein is stable but is not incorporated efficiently into the sarcomere. The transgenic muscle fibers showed a leftward shift in the pCa2+-force curve and, importantly, their power output was reduced. Additionally, expression of the mutant protein leads to decreased levels of endogenous MyBP-C, resulting in a striking pattern of sarcomere disorganization and dysgenesis.
