Abstract
The dermal striated muscle panniculus carnosus (PC), prevalent in lower mammals with remnants in humans, is highly regenerative, and whose function is purported to be linked to defence and shivering thermogenesis. Given the heterogeneity of responses of different muscles to disease, we set out to characterize the PC in wild-type and muscular dystrophic mdx mice. The mouse PC contained mainly fast-twitch type IIB myofibers showing body wide distribution. The PC exemplified heterogeneity in myofiber sizes and a prevalence of central nucleated fibres (CNFs), hallmarks of regeneration, in wild-type and mdx muscles, which increased with age. PC myofibers were hypertrophic in mdx compared to wild-type mice. Sexual dimorphism was apparent with a two-fold increase in CNFs in PC from male versus female mdx mice. To evaluate myogenic potential, PC muscle progenitors were isolated from 8-week old wild-type and mdx mice, grown and differentiated for 7-days. Myogenic profiling of PC-derived myocytes suggested that male mdx satellite cells (SCs) were more myogenic than female counterparts, independent of SC density in PC muscles. Muscle regenerative differences in the PC were associated with alterations in expression of calcium handling regulatory proteins. These studies highlight unique aspects of the PC muscle and its potential as a model to study mechanisms of striated muscle regeneration in health and disease.
Highlights
The dermal striated muscle panniculus carnosus (PC), prevalent in lower mammals with remnants in humans, is highly regenerative, and whose function is purported to be linked to defence and shivering thermogenesis
Murine skin is composed of multiple layers from the outer epidermis, dermis, panniculus adiposus (PA) and a thin 3–5 myofiber wide (~100 μm) striated muscle layer, located between the PA and interstitial connective tissue (ICT) layers on the dorsum of mice called the panniculus carnosus (PC) (Fig. 1A)
The muscle genotype of mouse tissues was confirmed by incubating sections with an anti-dystrophin antibody, where wild-type PC tissues were immunopositive for dystrophin in the surrounding sarcolemma, and mdx PC muscle sections were negative for dystrophin (Fig. 1C)
Summary
The dermal striated muscle panniculus carnosus (PC), prevalent in lower mammals with remnants in humans, is highly regenerative, and whose function is purported to be linked to defence and shivering thermogenesis. Given the heterogeneity of responses of different muscles to disease, we set out to characterize the PC in wild-type and muscular dystrophic mdx mice. Muscle regenerative differences in the PC were associated with alterations in expression of calcium handling regulatory proteins These studies highlight unique aspects of the PC muscle and its potential as a model to study mechanisms of striated muscle regeneration in health and disease. The more commonly described limb muscles degenerate with greater frequency in DMD20 These dissimilarities in susceptibility to muscle degeneration have in part been attributed to intrinsic differences including superior calcium homeostasis due to higher levels of calcium buffering/regulatory proteins in the degenerative resistant muscles[21,22,23]
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