SAGE Analysis of Genes Differentially Expressed in Presymptomatic TgSOD1G93A Transgenic Mice Identified Cellular Processes Involved in Early Stage of ALS ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-12-02

AUTHORS

Michel Guipponi, Qiao-Xin Li, Lavinia Hyde, Tim Beissbarth, Gordon K. Smyth, Colin L. Masters, 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 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. More... »

PAGES

172-182

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12031-009-9317-1

DOI

http://dx.doi.org/10.1007/s12031-009-9317-1

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19953340


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