title: Myofiber branching rather than myofiber hyperplasia contributes to muscle hypertrophy in mdx mice.
abstract: BACKGROUND
  Muscle hypertrophy in the mdx mouse model of Duchenne muscular dystrophy (DMD) can partially compensate for the loss of dystrophin by maintaining peak force production. Histopathology examination of the hypertrophic muscles suggests the hypertrophy primarily results from the addition of myofibers, and is accompanied by motor axon branching. However, it is unclear whether an increased number of innervated myofibers (myofiber hyperplasia) contribute to muscle hypertrophy in the mdx mice.
  
  
  METHODS
  To better understand the cellular mechanisms of muscle hypertrophy in mdx mice, we directly compared the temporal progression of the dystrophic pathology in the extensor digitorum longus (EDL) muscle to myofiber number, myofiber branching, and innervation, from 3 to 20 weeks of age.
  
  
  RESULTS
  We found that a 28% increase in the number of fibers in transverse sections of muscle correlated with a 31% increase in myofiber branching. Notably, the largest increases in myofiber number and myofiber branching occurred after 12 weeks of age when the proportion of myofibers with central nuclei had stabilized and the mdx mouse had reached maturity. The dystrophic pathology coincided with profound changes to innervation of the muscles that included temporary denervation of necrotic fibers, fragmentation of synapses, and ultra-terminal axon sprouting. However, there was little evidence of synapse formation in the mdx mice from 3 to 20 weeks of age. Only 4.4% of neuromuscular junctions extended ultra-terminal synapses, which failed to mature, and the total number of neuromuscular junctions remained constant.
  
  
  CONCLUSIONS
  Muscle hypertrophy in mdx mice results from myofiber branching rather than myofiber hyperplasia.
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA 98195-7720, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Faber
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA 98195-7720, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Hall
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA 98195-7720, USA ; Department of Biochemistry, University of Washington, Seattle, WA 98195-7720, USA ; Department of Medicine, University of Washington, Seattle, WA 98195-7720, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Chamberlain
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA 98195-7720, USA.
authors.forename: Glen B
authors.initials: GB
authors.lastname: Banks
keywords: Duchenne muscular dystrophy; Fiber branching; Hypertrophy; Inflammation; Innervation; Neuromuscular synapse; Skeletal muscle