Abstract
BackgroundPrions 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.ResultsWe 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.ConclusionOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1884-7) contains supplementary material, which is available to authorized users.
Highlights
Prions diseases are fatal neurodegenerative diseases of mammals
We show that Rat-Adapted Scrapie (RAS) is a powerful tool for an -omics based approach to decipher the molecular impact of prion disease in vivo, with applicability to the molecular mechanisms of disease and biomarker discovery
Development of rat-adapted scrapie To develop a rat-adapted strain of prion disease, we introduced 6 different prion disease agents, Chandler/ Rocky Mountain Lab (RML) from mice, Stetsonville transmissible mink encephalopathy (TME), Hyper from hamsters, skunk-adapted Transmissible Mink Encephalopathy [10] (TME) and Chronic Wasting Disease (CWD) from wild type and 96S deer [1, 10,11,12,13] into rats (Fig. 1)
Summary
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. Prion diseases are an unusual class of fatal, transmissible, neurodegenerative disorders that affect the mammalian central nervous system They are caused by the accumulation of an abnormal conformation of the normal host encoded cellular prion protein, PrPC. Laboratory investigation of prion diseases typically relies upon rodents, which can be infected with natural isolates of scrapie [1] albeit with some difficulty as ovid scrapie isolates need time to adapt to rodents. This adaptation is characteristic of interspecies transmission of prion infections and reflects the molecular adaptation that must occur to allow interaction between exogenous foreign PrPSc and host PrPC molecules, selecting for conformations which exhibit efficient template-directed prion-specific folding.
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