NR AXXL
AU Tang,Y.; Xiang,W.; Kretzschmar,H.A.; Windl,O.
TI Gene Expression Profiling during the Progression of BSE in Cattle
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.175
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
The molecular pathogenesis of TSEs is still not understood. The aims of this study were to elucidate the effect of prion pathogenesis on gene expression and to identify differentially regulated genes during the progression of BSE infection in cattle. We have analyzed brain tissue from time course samples (6, 21, 27, 36, 39 months p.i.) of cattle orally infected with BSE as well as terminally ill animals and healthy controls.
The microarray analysis was carried out using Affymetrix Bovine Genome GeneChips, which contained probes for 24,128 sets of transcripts. The data were normalized and analyzed using the GeneSpring software. Clustering analysis showed that there is a correlation between the disease progression and expression patterns. The mRNA of 205 genes was found to be differentially regulated by ANOVA with a p-value cutoff being 0.05. To validate the micoarray data, quantitative reverse transcriptase-PCR (rtPCR) of six genes was carried out and the rtPCR showed similar profiles to those of microarrays analysis.
Many of these 205 genes encode proteins involved in immune response, apoptosis, cell adhesion, stress response and transcription. Several genes and their protein products were already described in previous studies as having a link with prion diseases. Amongst them are s100 proteins, 14-4-4 proteins, collagen, integrin, the major histocompatibility complex and ribosomal proteins. The combination of ANOVA with fold change analysis revealed that most changes in gene expression occur between the negative controls and the animals 21 month post incubation, suggesting that there are many pathogenic processes in the animal brain prior to the clinical onset of BSE. This is consistent with the findings of gene expression studies in TSE-infected mice as well as with findings of early cognitive deficits and neurophysiological dysfunction in the similar murine TSE-models. The diagnostic potential of TSE-specific gene expression profiles is currently under evaluation.
AD Y. Tang, O. Windl, Veterinary Laboratories Agency, UK; W. Xiang, H.A. Kretzschmar, Ludwig-Maximilians University, Center for Neuropathology and Prion Research, Germany
SP englisch
PO Schottland