Identification of central nervous system genes involved in the host response to the scrapie agent during preclinical and clinical infection.
Genes that are expressed differentially in the central nervous system of mice during infection with mouse-adapted scrapie agents were identified in this study. cDNA microarrays were used to examine gene-expression profiles at early, middle (preclinical) and late (clinical) time points after inoculation. A number of genes that showed significant changes in expression during the clinical stage of disease were identified. Of these, 138 were upregulated and 20 were downregulated. A smaller number of genes showed differential expression at the early and middle stages of the disease time course. These genes are interesting, as they may reflect biological processes that are involved in the molecular pathogenesis of the prion agent. At present, little is known about the early events in the disease process that trigger neurodegeneration. Perhaps most interestingly, one group of genes that exhibited decreased expression in all tested stages of the disease was identified in this study. This cluster included four transcripts representing haematopoietic system-related genes, which suggests that the haematopoietic system is involved in the disease process from an early stage.
Division of Host Genetics and Prion Diseases, National Microbiology Laboratory, Health Canada, Winnipeg, MB, Canada R3E 3R2.
Stephanie
S
Booth
Institute for Biodiagnostics, National Research Council Canada, Winnipeg, MB, Canada R3B 1Y6.
Christopher
C
Bowman
Institute for Biodiagnostics, National Research Council Canada, Winnipeg, MB, Canada R3B 1Y6.
Richard
R
Baumgartner
Division of Host Genetics and Prion Diseases, National Microbiology Laboratory, Health Canada, Winnipeg, MB, Canada R3E 3R2.
Garrett
G
Sorensen
Division of Host Genetics and Prion Diseases, National Microbiology Laboratory, Health Canada, Winnipeg, MB, Canada R3E 3R2.
Catherine
C
Robertson
Division of Host Genetics and Prion Diseases, National Microbiology Laboratory, Health Canada, Winnipeg, MB, Canada R3E 3R2.
Michael
M
Coulthart
Division of Host Genetics and Prion Diseases, National Microbiology Laboratory, Health Canada, Winnipeg, MB, Canada R3E 3R2.
Clark
C
Phillipson
Institute for Biodiagnostics, National Research Council Canada, Winnipeg, MB, Canada R3B 1Y6.
Rajmund L
RL
Somorjai
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D006413:Hematopoietic System; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D012608:Scrapie / Q000235:genetics* / Q000473:pathology