Transcriptomic responses to prion disease in rats.
BACKGROUND
Prions diseases are fatal neurodegenerative diseases of mammals. While the molecular responses to prion infection have been extensively characterized in the laboratory mouse, little is known in other rodents. To explore these responses and make comparisons, we generated a prion disease in the laboratory rat by successive passage beginning with mouse RML prions.


RESULTS
We describe the accumulation of rat prions, associated pathology and the transcriptional impact throughout the disease course. Comparative transcriptional profiling between laboratory mice and rats suggests that similar molecular and cellular processes are unfolding in response to prion infection. At the level of individual transcripts, however, variability exists between mice and rats and many genes deregulated by prion infection in mice are not affected in rats.


CONCLUSIONS
Our findings detail the molecular responses to prion disease in the rat and highlight the usefulness of comparative approaches to understanding neurodegeneration and prion diseases in particular.
Department of Agricultural, Food and Nutritional Science, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, T6G 2M6, Canada.
Allen
A
Herbst
Department of Biological Sciences, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, T6G 2M6, Canada.
Anthony
A
Ness
Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, 53706, USA.
Chad J
CJ
Johnson
Department of Biological Sciences, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, T6G 2M6, Canada.
Debbie
D
McKenzie
Department of Agricultural, Food and Nutritional Science, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, T6G 2M6, Canada. Judd.Aiken@ualberta.ca.
Judd M
JM
Aiken
D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000235:genetics / Q000378:metabolism; D051381:Rats; D059467:Transcriptome
D018621:PrPC Proteins; D011328:Prions