NR AUSJ
AU Xiang,W.; Hummel,M.; Mitteregger,G.; Pace,C.; Windl,O.; Mansmann,U.; Kretzschmar,H.A.
TI Gene Expression Alterations in Scrapie-Infected Mouse Brains
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Poster: Pathogenese/Infektion PATH-10
PT Konferenz-Poster
AB The pathogenesis of prion disease is so far insufficiently understood. The aims of this study were to identify the differentially regulated genes during prion disease and to find the abnormal intracellular or intercellular events that may be responsible for the pathogenesis of prion disease. We applied Affymetrix MOE430A microarrays containing more than 22,000 transcripts and studied the global gene expression profiles in scrapie-infected mouse brains. For scrapie-infection, the mice were intracerebrally inoculated with 30 µl of a 10% brain homogenate of mice infected with mouse-adapted scrapie, ME7. We first compared gene expression in brains of scrapie-infected mice at the terminal stage of disease with gene expression in brains of control animals and identified genes which showed increased expression at the terminal stage of disease. Among these genes, the up-regulation of genes encoding proteins for proteolyses and immune response was conspicuous (Xiang et al. J. Virol. 2004, 78: 11051-11060). As the abnormalities in gene expression observed in mouse brains at terminal stage may partially represent secondary responses that develop during later stages of disease, it is interesting to reveal the early events in the disease process that may trigger neurodegeneration. To this end, we extended our gene profiling study to include ME7-infected mice at pre-clinical and clinical time points (90 -150 dpi) and compared gene expression in brains of these mice with that in brains of time-matched, mock-infected mice. Using a test of statistical significance ANOVA, we identified over 400 genes that showed changes in expression over the time course of infection. Gene ontology analysis revealed the major biological processes in which the differentially expressed genes are involved, including sterol metabolism. In addition, we identified several interesting clusters of genes that showed different expression patterns between pre-clinical and clinical stages of disease. The findings of this study shed light on the complex molecular events that occur during prion disease and offer a data resource for the biomarker selection.
AD Wei Xiang, Gerda Mitteregger, Claudia Pace, Hans A. Kretzschmar, Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Germany; Manuela Hummel, Ulrich Mansmann, Department of Medical Informatics, Biometrics, and Epidemiology, Ludwig-Maximilians-University, Munich, Germany; Otto Windl, Veterinary Laboratories Agency, Weybridge, United Kingdom
SP englisch
PO Deutschland
EA Übersicht, Details 1, Details 2
OR Tagungsband