Journal of Molecular Neuroscience

, Volume 41, Issue 1, pp 172–182

SAGE Analysis of Genes Differentially Expressed in Presymptomatic TgSOD1G93A Transgenic Mice Identified Cellular Processes Involved in Early Stage of ALS Pathology

  • Michel Guipponi
  • Qiao-Xin Li
  • Lavinia Hyde
  • Tim Beissbarth
  • Gordon K. Smyth
  • Colin L. Masters
  • Hamish S. Scott
Article

DOI: 10.1007/s12031-009-9317-1

Cite this article as:
Guipponi, M., Li, QX., Hyde, L. et al. J Mol Neurosci (2010) 41: 172. doi:10.1007/s12031-009-9317-1

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition in which motor neurons of the spinal cord and motor cortex degenerate, resulting in progressive paralysis. Transgenic mice expressing human mutant Cu/Zn superoxide dismutase-1 (SOD1) present a pathology that is very similar to that seen in human ALS patients. Using serial analysis of gene expression, we investigated the effects of mutant human SOD1 protein on global gene expression in the spinal cord and lower brain stem of presymptomatic TgSOD1G93A transgenic mice. One hundred twenty transcripts were found to be significantly dysregulated in the presence of mutant SOD1 protein, 79 being down-regulated and 41 up-regulated. Quantitative RT-PCR was used to confirm the differential expression of nine of these genes. Immunohistochemistry analysis on spinal cord sections revealed that dysregulation of these mutant SOD1-induced molecular pathways are concomitant to the appearance of discrete signs of neuropathology including neuronal loss, elevated gliosis, and ubiquitin-positive deposits. Altogether, our data showed that early signs of neuropathology in the SOD1 mutant mice are accompanied by altered expression of genes involved in various biological processes including apoptosis, oxidative stress, ATP biosynthesis, myelination, and axonal transport.

Keywords

Amyotrophic lateral sclerosis SOD1G93A Serial analysis of gene expression (SAGE) Transgenic mice Spinal cord 

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Michel Guipponi
    • 1
    • 7
  • Qiao-Xin Li
    • 2
    • 3
  • Lavinia Hyde
    • 1
  • Tim Beissbarth
    • 4
  • Gordon K. Smyth
    • 4
  • Colin L. Masters
    • 3
  • Hamish S. Scott
    • 5
    • 6
  1. 1.Division of Molecular MedicineThe Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  2. 2.Department of PathologyUniversity of MelbourneParkvilleAustralia
  3. 3.The Mental Health Research InstituteParkville3052Australia
  4. 4.Division of BioinformaticsThe Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  5. 5.Department of Molecular PathologyThe Centre for Cancer Biology, Institute of Medical and Veterinary Science and The Hanson InstituteAdelaideAustralia
  6. 6.Adelaide Cancer Research Institute, The School of MedicineUniversity of AdelaideAdelaideAustralia
  7. 7.Division of Medical GeneticsUniversity Hospital of GenevaChêne-BourgSwitzerland

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