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October 1, 1998Journal of Clinical InvestigationOpen Access

A mouse model of myosin binding protein C human familial hypertrophic cardiomyopathy.

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Population

Transgenic mice expressing varying amounts of a mutated MyBP-C or wild-type MyBP-C, and non-transgenic…

Comparison

Transgenic expression of truncated MyBP-C or… vs Non-transgenic littermates and mice expressing…

Design

Preclinical

Follow-up

up to 25 weeks (some observations up to 7 months)

Key result

Expression of a truncated MyBP-C lacking myosin and titin binding domains in transgenic mice led to sarcomere disorganization, increased Ca2+ sensitivity, and decreased maximum power output.

Authors

QYQi YangASAtsushi SanbeHOHanna Osińska

Discussion

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Overview

Offers a mouse model for HCM sarcomere defects; leaves open translation to human disease mechanisms and therapies.

Structured PICO

P
Population
Transgenic mice expressing varying amounts of a mutated MyBP-C (lacking myosin and titin binding domains) or wild-type MyBP-C, and non-transgenic littermates.
I
Intervention
Transgenic expression of truncated MyBP-C (MyBP-C.mut1) or wild-type MyBP-C (MyBP-C.wt) under the cardiac-specific α-MyHC promoter.
C
Comparator
Non-transgenic (NTG) littermates and mice expressing wild-type MyBP-C.
O
Outcome
Sarcomere organization, protein incorporation, and mechanical properties of skinned fiber strips (pCa2+-force curve, power output).surrogate

Expression of truncated MyBP-C in a transgenic mouse model leads to sarcomere disorganization, increased calcium sensitivity, and reduced power output, providing a mechanistic model for familial hypertrophic cardiomyopathy.

Limitations

  • Lack of a large, aged cohort of animals suitable for detailed morphometric and stress exercise analyses to define late-onset hypertrophic processes.

Cite This Study

Yang et al. (1998) studied Familial hypertrophic cardiomyopathy (FHC). Transgenic expression of mutated MyBP-C (MyBP-C.mut1) vs. Nontransgenic littermates and wild-type MyBP-C transgenic mice was evaluated on Sarcomere organization and cardiac fiber mechanics (Ca2+ sensitivity and power output). Expression of a truncated MyBP-C lacking myosin and titin binding domains in transgenic mice led to sarcomere disorganization, increased Ca2+ sensitivity, and decreased maximum power output.

synapsesocial.com/papers/6a163073b6d9529585c1fa32https://doi.org/10.1172/jci3880
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