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https://hdl.handle.net/2440/59410
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Type: | Journal article |
Title: | SAGE analysis of genes differentially expressed in presymptomatic TgSOD1(G93A) transgenic mice identified cellular processes involved in early stage of ALS pathology |
Author: | Guipponi, M. Li, Q. Hyde, L. Beissbarth, T. Smyth, G. Masters, C. Scott, H. |
Citation: | Journal of Molecular Neuroscience, 2010; 41(1):172-182 |
Publisher: | Humana Press Inc |
Issue Date: | 2010 |
ISSN: | 0895-8696 1559-1166 |
Statement of Responsibility: | Michel Guipponi, Qiao-Xin Li, Lavinia Hyde, Tim Beissbarth, Gordon K. Smyth, Colin L. Masters and Hamish S. Scott |
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 TgSOD1(G93A) 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 |
Rights: | © Springer |
DOI: | 10.1007/s12031-009-9317-1 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/219176 http://purl.org/au-research/grants/nhmrc/257501 http://purl.org/au-research/grants/nhmrc/215201 http://purl.org/au-research/grants/nhmrc/257529 http://purl.org/au-research/grants/nhmrc/208978 |
Published version: | http://dx.doi.org/10.1007/s12031-009-9317-1 |
Appears in Collections: | Aurora harvest Medicine publications |
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