Properties of regenerated mouse extensor digitorum longus muscle following notexin injury

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Abstract
New Findings: What is the central question of this study? In dystrophinopathies, regenerated muscles contain branched fibres. We have hypothesized that, once a threshold is reached, part of the susceptibility of dystrophic muscle to damage is due to the presence of branched fibres, not the absence of dystrophin. Here, we explore the novel question: ‘Does dystrophin‐positive, regenerated muscle containing branched fibres also show an increased susceptibility to contraction‐induced damage?’ What is the main finding and its importance? One round of notexin regeneration produces a dystrophin‐positive muscle containing 29% branched fibres, which is below threshold and not more susceptible than wild‐type muscle to damage. This muscle would serve as an ideal control for young mdx mice. Muscles of mdx mice are known to be more susceptible to contraction‐induced damage than wild‐type muscle. However, it is not clear whether this is because of dystrophin deficiency or because of the abnormal branching morphology of dystrophic muscle fibres. This distinction has an important bearing on our traditional understanding of the function of dystrophin as a mechanical stabilizer of the sarcolemma. In this study, we address the question: ‘Does dystrophin‐positive, regenerated muscle containing branched fibres also show an increased susceptibility to contraction‐induced damage?’ We produced a model of fibre branching by injecting dystrophin‐positive extensor digitorum longus muscles with notexin. The regenerated muscle was examined at 21 days postinjection. Notexin‐injected muscle contained 29% branched fibres and was not more susceptible to damage from mild eccentric contractions than contralateral saline‐injected control muscle. Regenerated muscles also had greater mass, greater cross‐sectional area and lower specific force than control muscles. We conclude that the number of branched fibres in this regenerated muscle is below the threshold needed to increase susceptibility to damage. However, it would serve as an ideal control for muscles of young mdx mice, allowing for clearer differentiation of the effects of dystrophin deficiency from the effects of fibre regeneration and morphology.
Funding Information
  • Goldstar grant from the University of New South Wales
  • National Health and Medical Research Council (NHMRC) (1002033)

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