Mammalian prion propagation in PrP transgenic Drosophila.
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Publication Date
2018-09-01Journal Title
Brain
ISSN
0006-8950
Publisher
Oxford University Press (OUP)
Volume
141
Issue
9
Pages
2700-2710
Language
eng
Type
Article
Physical Medium
Print
Metadata
Show full item recordCitation
Thackray, A. M., Andréoletti, O., & Bujdoso, R. (2018). Mammalian prion propagation in PrP transgenic Drosophila.. Brain, 141 (9), 2700-2710. https://doi.org/10.1093/brain/awy183
Abstract
Mammalian prions propagate by template-directed misfolding and aggregation of normal cellular prion related protein PrPC as it converts into disease-associated conformers collectively referred to as PrPSc. Mammalian species may be permissive for prion disease because these hosts have co-evolved specific co-factors that assist PrPC conformational change and prion propagation. We have tested this hypothesis by examining whether faithful prion propagation occurs in the normally PrPC-null invertebrate host Drosophila melanogaster. Ovine PrP transgenic Drosophila exposed at the larval stage to ovine scrapie showed a progressive accumulation of transmissible prions in adult flies. Strikingly, the biological properties of distinct ovine prion strains were maintained during their propagation in Drosophila. Our observations show that the co-factors necessary for strain-specific prion propagation are not unique to mammalian species. Our studies establish Drosophila as a novel host for the study of transmissible mammalian prions.
Keywords
Animals, Animals, Genetically Modified, Mice, Transgenic, Sheep, Humans, Mice, Drosophila melanogaster, Prion Diseases, Scrapie, Disease Models, Animal, Drosophila Proteins, Prions, Prion Proteins
Sponsorship
This work was supported by funds from the NC3Rs Project (Grant NC/K000462/1).
Funder references
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/K000462/1)
Identifiers
External DOI: https://doi.org/10.1093/brain/awy183
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280007
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International
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