Restricted expression of mutant SOD1 in spinal motor neurons and interneurons induces motor neuron pathology

Neurobiol Dis. 2008 Mar;29(3):400-8. doi: 10.1016/j.nbd.2007.10.004. Epub 2007 Oct 23.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons (MNs). Approximately 10% of ALS cases are familial (known as FALS), and approximately 20% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase type 1 (SOD1). Mutant (MT) SOD1 induces FALS as a result of a toxicity that remains poorly defined. Several studies suggest that the toxicity involves a non-cell autonomous mechanism. In this study, we generated transgenic mice that had a restricted and repressible expression of MTSOD1 in spinal MNs and interneurons. Although the transgenic mice were not weak, they weighed less than control mice and had pathological and immunohistochemical abnormalities of MNs confined to cells that expressed MTSOD1. These results suggest that MTSOD1-induced MN degeneration is at least partly cell autonomous. Mouse models similar to the one presented here will be valuable for spatially and temporally controlling expression of mutant genes involved in neurodegenerative diseases.

Publication types

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

MeSH terms

  • Animals
  • Gene Expression Regulation, Enzymologic / physiology*
  • Humans
  • Interneurons / enzymology*
  • Interneurons / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Neurons / enzymology*
  • Motor Neurons / pathology
  • Mutation / physiology*
  • Superoxide Dismutase / biosynthesis*
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / physiology
  • Superoxide Dismutase-1

Substances

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