Journal of Molecular Neuroscience

, Volume 41, Issue 1, pp 172–182 | Cite as

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 LiEmail author
  • Lavinia Hyde
  • Tim Beissbarth
  • Gordon K. Smyth
  • Colin L. Masters
  • Hamish S. Scott


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.


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



This work was supported by National Health and Medical Research Council fellowships (171601 and 461204 to H.S.S); National Health and Medical Research Council Grants 219176, 257501, 215201, and 257529 (to H.S.S. and G.K.S.) and 208978 (to CLM and QXL); a grant in aid from the Motor Neurone Disease Research Institute of Australia (MLG, HSS and QXL); and a fellowship from the Deutsche Forschungsgemeinschaft (to T.B.).

DNA sequencing of SAGE libraries was performed by the Australian Genome Research Facility, which was established through the Commonwealth-funded Major National Research Facilities program.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Michel Guipponi
    • 1
    • 7
  • Qiao-Xin Li
    • 2
    • 3
    Email author
  • 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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