Early decrease of mitochondrial DNA repair enzymes in spinal motor neurons of presymptomatic transgenic mice carrying a mutant SOD1 gene

Brain Res. 2007 May 30:1150:182-9. doi: 10.1016/j.brainres.2007.02.057. Epub 2007 Mar 1.

Abstract

Growing evidence has recently shown that mutant SOD1 accumulate in the mitochondria and cause vacuolation in transgenic mice carrying mutant SOD1, an animal model of amyotrophic lateral sclerosis (ALS). In this study, the expressions of DNA repair enzymes, oxoguanine glycosylase 1 (ogg1), DNA polymerase beta (polbeta), and DNA polymerase gamma (polgamma) were examined in transgenic mice with an ALS-linked mutant SOD1 gene, a valuable model for human ALS. In presymptomatic Tg mice, the nuclear form of ogg1 was upregulated, whereas mitochondrial ogg1 remained at the same level. DNA polymerase was selectively downregulated in the mitochondria. This study suggests an impaired protective mechanism against oxidative stress in mitochondria. The expressions of these enzymes are predominant in spinal motor neurons, suggesting a mechanism of selective motor neuron death in this animal model of ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Glycosylases / metabolism
  • DNA Polymerase beta / metabolism
  • DNA Polymerase gamma
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • DNA-Directed DNA Polymerase
  • Gene Expression Regulation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Neurons / enzymology*
  • Mutation*
  • Spinal Cord / cytology*
  • Superoxide Dismutase / genetics*

Substances

  • SOD1 G93A protein
  • Superoxide Dismutase
  • DNA Polymerase beta
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • DNA Glycosylases
  • Ogg1 protein, mouse
  • DNA Repair Enzymes