Transcriptomic responses to prion disease in rats.
Ontology highlight
ABSTRACT: 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.Conclusion
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.
SUBMITTER: Herbst A
PROVIDER: S-EPMC4560926 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
Publications
Transcriptomic responses to prion disease in rats.
Herbst Allen A Ness Anthony A Johnson Chad J CJ McKenzie Debbie D Aiken Judd M JM
BMC genomics 20150905
<h4>Background</h4>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.<h4>Results</h4>We describe the accumulation of rat prions, associated pathology and the transcriptional impact throug ...[more]
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Project description:While prion infections have been extensively characterized in the laboratory mouse, little is known regarding the molecular responses to prions in other rodents. To explore these responses and make comparisons, we generated a prion disease in the laboratory rat by successive passage of mouse RML prions. Here we describe the accumulation of prions and associated pathology in the rat and describe the transcriptional impact throughout prion disease. Comparative transcriptional profiling between laboratory mice and rats suggests that similar molecular 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 in mouse scrapie are not affected in rats. Notwithstanding these differences, many transcriptome responses are conserved between mice and rats infected with scrapie. Our findings highlight the usefulness of comparative approaches to understanding neurodegeneration and prion diseases in particular. We Adapted RML Mouse Scrapie into Rats and measured the resulting gene expression changes in brain as a result of disease progression. Rats were infected by intracranial inoculation with prion isolates obtained by adaptation of mouse RML scrapie prions into rats. Brain samples were collected from third and fourth passage infected rats and age-matched controls at specified timepoints and gene expression profiles obtained. For each time point, 3 diseased and control brain samples were profiled.
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