Time course of preferential motor unit loss in the SOD1 G93A mouse model of amyotrophic lateral sclerosis

Neurobiol Dis. 2007 Nov;28(2):154-64. doi: 10.1016/j.nbd.2007.07.003. Epub 2007 Jul 10.


Electromyographical analyses of pre-symptomatic motor unit loss in the SOD1 G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS) have yielded contradictory findings as to the onset and time course. We recorded hindlimb muscle and motor unit isometric forces to determine motor unit number and size throughout the life span of the mice. Motor unit numbers in fast-twitch tibialis anterior, extensor digitorum longus and medial gastrocnemius muscles declined from 40 days of age, 50 days before reported overt symptoms and motoneuron loss. Motor unit numbers fell after overt symptoms in the slow-twitch soleus muscle. Muscle forces declined in parallel with motor unit numbers, indicating little or no functional compensation by sprouting. Early muscle-specific decline was due to selective preferential vulnerability of large, fast motor units, innervated by large motoneurons. Large motoneurons are hence the most vulnerable in ALS with die-back occurring prior to overt symptoms. We conclude that size of motoneurons, their axons, and their motor unit size are important determinants of motoneuron susceptibility in ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / enzymology
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Axons / enzymology
  • Axons / pathology
  • Cell Death / genetics
  • Cell Size
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Neurons / enzymology*
  • Motor Neurons / pathology
  • Muscle Contraction / genetics
  • Muscle Fibers, Fast-Twitch / enzymology
  • Muscle Fibers, Fast-Twitch / pathology
  • Muscle Fibers, Slow-Twitch / enzymology
  • Muscle Fibers, Slow-Twitch / pathology
  • Muscle Strength / genetics
  • Muscle, Skeletal / innervation*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology*
  • Nerve Degeneration / enzymology
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology*
  • Neuromuscular Junction / pathology
  • Neuromuscular Junction / physiopathology*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1
  • Time Factors
  • Wallerian Degeneration / enzymology
  • Wallerian Degeneration / pathology
  • Wallerian Degeneration / physiopathology


  • SOD1 protein, human
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1