Abnormalities in structure and function of limb skeletal muscle fibres of dystrophic mdx mice

Abstract

In this study we have shown that the skeletal muscle fibres from adult (older than 26 weeks) mdx mice have gross structural deformities. We have characterized the onset and age dependence of this feature in mdx mice. The three dimensional structure of these deformities has been visualized in isolated fibres and the orientation of these deformities was determined within the muscle by confocal laser scanning microscopy. We have also shown that the occurrence of morphologically abnormal fibres is greater in muscles with longer fibres (extensor digitorum longus (EDL) and soleus, 6-7.3 mm long), than in muscles with shorter fibres (flexor digitorum brevis (FDB), 0.3-0.4 mm long). A population of post-degenerative fibres, with both central and peripheral nuclei coexistent along the length of the fibre, has also been identified in the muscles studied. We showed that a mild protocol of lengthening (eccentric) contractions (the muscle was stretched by 12% during a tetanic contraction) caused a major reduction in the maximal tetanic force subsequently produced by mdx EDL muscle. In contrast, maximal tetanic force production in normal soleus, normal EDL and mdx soleus muscles was not altered by this protocol. We suggest that the deformed fast glycolytic fibres which are found in adult mdx EDL but not in adult mdx soleus muscles are the population of fibres damaged by the lengthening protocol.

Membrane potential, resting calcium and calcium transients in isolated muscle fibres from normal and dystrophic mice.

“…Of 580 mdx FDB skeletal muscle fibres viewed in this study only four had deformities; this is in agreement with our previous study where in mice younger than 14 weeks of age less than 5 % of the mdx FDB fibres were deformed (Head et al 1992).…”

New insights on contraction efficiency in patients with Duchenne muscular dystrophy

“…These results support the role of dystrophin for force transmission from the cytoskeleton to extracellular matrix at the level of both muscle sarcomere and the myotendinous junction (36). Second, structural abnormalities such as sarcomere disconnections (8), malformed/branched fibers (13), and detached fibers from tendons (13), may lead to an alteration of the longitudinal transmission from the force-generating structures to the myotendinous junction.…”

A gene for speed: contractile properties of isolated whole EDL muscle from an α-actinin-3 knockout mouse

“…Branched fibers are found in processes involving continuous degeneration and regeneration of muscle, such as in the X-linked recessive condition of Duchenne muscular dystrophy. In mice with an equivalent condition, muscles contain a large proportion of branched fibers, and these fibers have centrally located nuclei, another feature of regenerating muscle (6).…”