title: SAGE analysis of genes differentially expressed in presymptomatic TgSOD1G93A transgenic mice identified cellular processes involved in early stage of ALS pathology.
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.
authors: Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3050, Australia. Michel.Guipponi@hcuge.ch
authors: Michel
authors: M
authors: Guipponi
authors: Qiao-Xin
authors: QX
authors: Li
authors: Lavinia
authors: L
authors: Hyde
authors: Tim
authors: T
authors: Beissbarth
authors: Gordon K
authors: GK
authors: Smyth
authors: Colin L
authors: CL
authors: Masters
authors: Hamish S
authors: HS
authors: Scott
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001369:Axons / Q000378:metabolism; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D049231:Saposins / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D003598:Cytoskeletal Proteins; C483344:Psap protein, mouse; C000606290:SOD1 protein, human; D049231:Saposins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1