title: Decrease of myofiber branching via muscle-specific expression of the olfactory receptor mOR23 in dystrophic muscle leads to protection against mechanical stress.
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.
authors.affiliation: Department of Pharmacology, Emory University, Atlanta, GA USA ; Present address: Department of Genetics, Stanford University, Stanford, CA USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pichavant
authors.affiliation: School of Applied Physiology, Georgia Institute of Technology, Atlanta, GA USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Burkholder
authors.affiliation: Department of Pharmacology, Emory University, Atlanta, GA USA ; 1510 Clifton Road, Room 5024, Atlanta, GA 30322 USA.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Pavlath
mesh_terms: D000367:Age Factors; D000818:Animals; D017609:Barium Compounds / Q000633:toxicity; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D002712:Chlorides / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D006824:Hybridization, Genetic; D008297:Male; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration; D013314:Stress, Mechanical; D015854:Up-Regulation
chemical_list: D017609:Barium Compounds; D002712:Chlorides; C118713:Olfr16 protein, mouse; D018035:Receptors, Odorant; C024986:barium chloride
keywords: Mechanical stress; Muscle regeneration; Muscular dystrophy; Myofiber branching; mOR23