No widespread induction of cell death genes occurs in pure motoneurons in an amyotrophic lateral sclerosis mouse model

Hum Mol Genet. 2005 Nov 1;14(21):3309-20. doi: 10.1093/hmg/ddi357. Epub 2005 Sep 28.


To identify candidate genes that may be involved in motoneuron degeneration, we combined laser capture microdissection with microarray technology. Gene expression in motoneurons was analyzed during the progression of the disease in transgenic SOD1(G93A) mice that develop motoneuron loss. Three major observations were made: first, there was only a small number of genes that were differentially expressed in motoneurons at a pre-symptomatic age (27 out of 34 000 transcripts). Secondly, there is an early specific up-regulation of the gene coding for the intermediate filament vimentin that is increased even further during disease progression. Using in situ hybridization and immunohistochemical analysis, we show that vimentin expression was not only elevated in motoneurons but that the protein formed inclusions in the motoneuron cytoplasm. Thirdly, a time-course analysis of the motoneurons at a symptomatic age (90 and 120 days) showed a modest de-regulation of only a few genes associated with cell death pathways; however, a massive up-regulation of genes involved in cell growth and/or maintenance was observed. This is the first description of the gene profile of SOD1(G93A) motoneurons during disease progression and unexpectedly, no widespread induction of cell death-associated genes was detected in motoneurons of SOD1(G93A) mice.

Publication types

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

MeSH terms

  • Age Factors
  • Amyotrophic Lateral Sclerosis / genetics*
  • Animals
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins / metabolism*
  • Gene Expression Profiling*
  • Gene Expression Regulation / genetics*
  • Immunohistochemistry
  • In Situ Hybridization
  • Inclusion Bodies / metabolism
  • Mice
  • Mice, Transgenic
  • Motor Neurons / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1
  • Vimentin / metabolism


  • Apoptosis Regulatory Proteins
  • Vimentin
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1