Transgenic mouse models of amyotrophic lateral sclerosis

Biochim Biophys Acta. 2006 Nov-Dec;1762(11-12):1013-24. doi: 10.1016/j.bbadis.2006.03.006. Epub 2006 Apr 21.


The discovery of missense mutations in the gene coding for the Cu/Zn superoxide dismutase 1 (SOD1) in subsets of familial cases was rapidly followed by the generation of transgenic mice expressing various forms of SOD1 mutants. The mice overexpressing high levels of mutant SOD1 mRNAs do develop motor neuron disease but unraveling the mechanisms of pathogenesis has been very challenging. Studies with mouse lines suggest that the toxicity of mutant SOD1 is unrelated to copper-mediated catalysis but rather to propensity of a subfraction of mutant SOD1 proteins to form misfolded protein species and aggregates. However, the mechanism of toxicity of SOD1 mutants remains to be elucidated. Involvement of cytoskeletal components in ALS pathogenesis is supported by several mouse models of motor neuron disease with neurofilament abnormalities and with genetic defects in microtubule-based transport. Here, we describe how transgenic mouse models have been used for understanding pathogenic pathways of motor neuron disease and for pre-clinical drug testing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / therapy*
  • Animals
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Intermediate Filaments / genetics
  • Intermediate Filaments / metabolism
  • Intermediate Filaments / pathology
  • Mice
  • Mice, Transgenic
  • Microtubules / physiology
  • Models, Neurological*
  • Motor Neurons / metabolism
  • Motor Neurons / pathology*
  • Mutation
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Vascular Endothelial Growth Factor A / genetics


  • Als2 protein, mouse
  • Guanine Nucleotide Exchange Factors
  • SOD1 protein, human
  • Vascular Endothelial Growth Factor A
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1