Decrease of myofiber branching via muscle-specific expression of the olfactory receptor mOR23 in dystrophic muscle leads to protection against mechanical stress

• Type of Material: Article
• Authors: Christophe Pichavant, Emory University; Thomas J. Burkholder, Georgia Institute of Technology; Grace Pavlath, Emory University
• Language: English
• Date: 2016-01-21
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Pichavant et al. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13395-016-0077-7
• Title of Journal or Parent Work: Skeletal Muscle
• ISSN: 2044-5040
• Volume: 6
• Issue: 1
• Start Page: 2
• End Page: 2
• Grant/Funding Information: This work was supported by grants to GKP from the Muscular Dystrophy Association (#186852) and NIH (AR061267).
• Keywords: Science & Technology; Mechanical stress; FIBERS; SATELLITE CELLS; MICE; mOR23; DUCHENNE MUSCULAR-DYSTROPHY; Muscle regeneration; Muscular dystrophy; Life Sciences & Biomedicine; Myofiber branching; MYOGENIC CELLS; Cell Biology; MDX MUSCLE; REGENERATION
• Research Categories: Biology, Physiology; Biology, Cell

Abstract

Background: Abnormal branched myofibers within skeletal muscles are commonly found in diverse animal models of muscular dystrophy as well as in patients. Branched myofibers from dystrophic mice are more susceptible to break than unbranched myofibers suggesting that muscles containing a high percentage of these myofibers are more prone to injury. Previous studies showed ubiquitous over-expression of mouse olfactory receptor 23 (mOR23), a G protein-coupled receptor, in wild type mice decreased myofiber branching. Whether mOR23 over-expression specifically in skeletal muscle cells is sufficient to mitigate myofiber branching in dystrophic muscle is unknown. Methods: We created a novel transgenic mouse over-expressing mOR23 specifically in muscle cells and then bred with dystrophic (mdx) mice. Myofiber branching was analyzed in these two transgenic mice and membrane integrity was assessed by Evans blue dye fluorescence. Results: mOR23 over-expression in muscle led to a decrease of myofiber branching after muscle regeneration in non-dystrophic mouse muscles and reduced the severity of myofiber branching in mdx mouse muscles. Muscles from mdx mouse over-expressing mOR23 significantly exhibited less damage to eccentric contractions than control mdx muscles. Conclusions: The decrease of myofiber branching in mdx mouse muscles over-expressing mOR23 reduced the amount of membrane damage induced by mechanical stress. These results suggest that modifying myofiber branching in dystrophic patients, while not preventing degeneration, could be beneficial for mitigating some of the effects of the disease process.