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June 19, 2013Human Molecular GeneticsOpen Access

Transgenic over-expression of cardiac α-actin in ACTC(Co)/KO mice resulted in 20 to 25% less myofibre force production and lower stiffness compared with age-matched wild-types.

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Population

ACTC/KO mouse model and age-matched wild-types

Comparison

Transgenic over-expression of cardiac α-actin in… vs Age-matched wild-type mice

Design

Preclinical

Key result

Transgenic over-expression of cardiac α-actin in ACTC(Co)/KO mice resulted in 20 to 25% less myofibre force production and lower stiffness compared with age-matched wild-types.

Authors

JOJulien OchalaHIHiroyuki IwamotoGRGianina Ravenscroft

Discussion

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Overview

Supports isoform effects on myofibre mechanics in mice; leaves open relevance to ACTA1 gene therapy design.

Structured PICO

P
Population
ACTC(Co)/KO mouse model (mimicking ACTA1 null mutations rescued by transgenic over-expression of cardiac α-actin in skeletal muscles) and age-matched wild-types
E
Exposure
Transgenic over-expression of cardiac α-actin in skeletal muscles
C
Comparator
Age-matched wild-type mice (expressing normal skeletal muscle α-actin)
O
Outcome
Myofibre force production, stiffness, and actin conformational changes (assessed via mechanical and X-ray diffraction pattern analyses of single membrane-permeabilized myofibres)surrogate

The presence of cardiac α-actin instead of skeletal muscle α-actin alters actin conformational changes and lowers myofibre force production, which has implications for designing gene therapies for ACTA1-based congenital myopathies.

Cite This Study

Ochala et al. (2013) studied Congenital myopathies (ACTA1 null mutations). Transgenic over-expression of cardiac α-actin vs. Age-matched wild-types was evaluated on Myofibre force production and stiffness. Transgenic over-expression of cardiac α-actin in ACTC(Co)/KO mice resulted in 20 to 25% less myofibre force production and lower stiffness compared with age-matched wild-types.

synapsesocial.com/papers/6a9619ac2765660692a78447https://doi.org/10.1093/hmg/ddt289
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