title: Transcriptome Profiling Following Neuronal and Glial Expression of ALS-Linked SOD1 in Drosophila.
abstract: Amyotrophic lateral sclerosis (ALS) generally is a late-onset neurodegenerative disease. Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene account for approximately 20% of familial ALS and 2% of all ALS cases. Although a number of hypotheses have been proposed to explain mutant SOD1 toxicity, the molecular mechanisms of the disease remain unclear. SOD1-linked ALS is thought to function in a non-cell-autonomous manner such that motoneurons are critical for the onset, and glia contribute to progression of the disease. Recently, it has been shown in Drosophila melanogaster that expression of human SOD1 in a subset of neuronal cells causes synaptic transmission defects, modified motor function, and altered sensitivity to compounds that induce oxidative stress. Here we used the Gal4-UAS (Upstream Activation Sequence) system to further characterize flies expressing wild-type Drosophila SOD1 (dSOD1) and the mutant human SOD1G85R(G85R) allele in motoneurons and glia. Cell-specific expression of both dSOD1 and G85R was found to influence lifespan, affect sensitivity to hydrogen peroxide, and alter lipid peroxidation levels. To better understand the genetic consequences of G85R expression in motoneurons and glia, we conducted microarray analysis of both young flies (5 days old) and old flies (45 days old) expressing G85R selectively in motoneurons or glia and concurrently in motoneurons and glia. Results from this microarray experiment identified candidate genes for further investigation and may help elucidate the individual and combined contributions of motoneurons and glia in ALS.
authors.affiliation: Department of Biology, University of Oklahoma, Norman, Oklahoma 73019.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Kumimoto
authors.affiliation: Department of Biology, University of Oklahoma, Norman, Oklahoma 73019.
authors.forename: Taylor R
authors.initials: TR
authors.lastname: Fore
authors.affiliation: Department of Biology, University of Oklahoma, Norman, Oklahoma 73019 zhangbing@missouri.edu.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
keywords: ALS; Drosophila; SOD1; glia; motoneuron
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