Scientific article

Cell death pathways differ in several mouse models with motoneurone disease: analysis of pure motoneurone populations at a presymptomatic age

Published inJournal of neurochemistry, vol. 98, no. 6, p. 1959-1972
Publication date2006-09
First online date2006-07-11

To identify candidate genes that are responsible for motoneurone degeneration, we combined laser capture microdissection with microarray technology. We analysed gene expression in pure motoneurones from two mouse mutants that develop motoneurone degeneration, progressive motor neuronopathy and wobbler. At a presymptomatic age, there was a significant differential expression of a restricted number of genes (25 and 72 in progressive motor neuronopathy and wobbler respectively, of 22 600 transcripts screened). We compared these results to our previous analyses in the copper-zinc superoxide dismutase mutant mouse (SOD1(G93A)) in which we observed a de-regulation of 27 genes. Some of these genes were de-regulated uniquely in one mouse mutant and some have already been identified in cell death pathways implicated in amyotrophic lateral sclerosis and animal models of motoneurone degeneration (i.e. de-regulation of intermediate filaments, axonal transport, the ubiquitin-proteasome system and excitotoxicity). One gene, vimentin, was differentially up-regulated in all mouse mutants; this main candidate gene has been confirmed by in situ hybridization and immunohistochemistry to be expressed in motoneurones in all mouse mutants. Furthermore, vimentin expression correlated with the state of motoneurone degeneration. These results identify early molecular changes that may be involved in the pathogenesis of motoneurones leading to cell death and favour a complex multipathway induction of the disease; surprisingly, there was no important modification in cell death-associated genes. This is the first study to show a clear difference in the genes that are de-regulated at an early stage in three different mouse models of motoneurone disease.

  • Animals
  • Animals, Newborn
  • Cell Death
  • Cell Separation / methods
  • Computer Systems
  • Cytoplasm / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Inclusion Bodies / pathology
  • Lasers
  • Mice
  • Mice, Neurologic Mutants
  • Microdissection
  • Motor Neuron Disease / genetics
  • Motor Neuron Disease / pathology
  • Motor Neuron Disease / physiopathology
  • Motor Neurons / metabolism
  • Nerve Degeneration / genetics
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Spinal Cord / pathology
  • Vimentin / genetics
  • Vimentin / metabolism
Citation (ISO format)
PERRIN, Florence E et al. Cell death pathways differ in several mouse models with motoneurone disease: analysis of pure motoneurone populations at a presymptomatic age. In: Journal of neurochemistry, 2006, vol. 98, n° 6, p. 1959–1972. doi: 10.1111/j.1471-4159.2006.04024.x
Main files (1)
Article (Published version)
ISSN of the journal0022-3042

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