Intrinsic laryngeal muscles are spared from myonecrosis in the mdx mouse model of Duchenne muscular dystrophy

Abstract

Intrinsic laryngeal muscles share many anatomical and physiological properties with extraocular muscles, which are unaffected in both Duchenne muscular dystrophy and mdx mice. We hypothesized that intrinsic laryngeal muscles are spared from myonecrosis in mdx mice and may serve as an additional tool to understand the mechanisms of muscle sparing in dystrophinopathy. Intrinsic laryngeal muscles and tibialis anterior (TA) muscle of adult and aged mdx and control C57Bl/10 mice were investigated. The percentage of central nucleated fibers, as a sign of muscle fibers that had undergone injury and regeneration, and myofiber labeling with Evans blue dye, as a marker of myofiber damage, were studied. Except for the cricothyroid muscle, none of the intrinsic laryngeal muscles from adult and old mdx mice showed signs of myofiber damage or Evans blue dye labeling, and all appeared to be normal. Central nucleation was readily visible in the TA of the same mdx mice. A significant increase in the percentage of central nucleated fibers was observed in adult cricothyroid muscle compared to the other intrinsic laryngeal muscles, which worsened with age. Thus, we have shown that the intrinsic laryngeal muscles are spared from the lack of dystrophin and may serve as a useful model to study the mechanisms of muscle sparing in dystrophinopathy.

Sarcoplasmic–endoplasmic–reticulum Ca2+‐ATPase and calsequestrin are overexpressed in spared intrinsic laryngeal muscles of dystrophin‐deficient mdx mice

“…19,46 We have previously reported that the ILM of mdx mice are spared from degeneration despite the lack of dystrophin. 30 In this study we observed that expression of the key calcium-regulatory proteins SERCA1 and calsequestrin is increased in dystrophic ILM. This supports the hypothesis that these muscles may have a better ability to maintain calcium homeostasis, which is correlated with muscle sparing.…”

“…1 We have demonstrated that intrinsic laryngeal muscles (ILM) are protected against myonecrosis in mdx mice. 30 Dystrophic extraocular muscles (EOM) are also spared in DMD, 2,27,31,36 possibly because of a greater ability to maintain calcium homeostasis compared with other striated muscles. 27 Other factors seem to be involved in EOM protection as well.…”

Estimation of the number and size of motor units in intrinsic laryngeal muscles using morphometric methods

“…However, our analysis did not include different segments of the nerve and axonal degeneration might be too fast to be detected at a given time point. Nevertheless, other factors may be involved in the remodeling of the human larynx such as sprouting and retraction of nerve terminals, which may occur at the neuromuscular junction in response to the laryngeal muscle fiber regeneration normally seen in aged humans (Malmgren et al, 2000) and mice (Marques et al, 2007). The synaptic rearrangement that is known to occur in old neuromuscular junctions may affect the number of MUs estimated by clinical methods (Gambino et al, 1990), but not by morphological methods because it does not necessarily involve axon loss.…”

Proteomic profiling of naturally protected extraocular muscles from the dystrophin-deficient mdx mouse

“…However, not all subtypes of skeletal muscles are affected in the same way in x-linked muscular dystrophy. For example, intrinsic laryngeal and certain distal muscle fibers, as well as extraocular muscle (EOM), are protected from a severely degenerative phenotype in dystrophic organisms [5][6][7][8][9][10][11]. Although the contractile efficiency of EOM is weakened in various muscle-related pathologies, such as myasthenia gravis, myasthenic syndromes, botulism, and myotonia congenita [12][13][14], they are usually spared in DMD patients [15][16][17].…”