Mammalian prion propagation in PrP transgenic Drosophila.
Oxford University Press (OUP)
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Thackray, A., Andréoletti, O., & Bujdoso, R. (2018). Mammalian prion propagation in PrP transgenic Drosophila.. Brain, 141 (9), 2700-2710. https://doi.org/10.1093/brain/awy183
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.
Animals, Animals, Genetically Modified, Mice, Transgenic, Sheep, Humans, Mice, Drosophila melanogaster, Prion Diseases, Scrapie, Disease Models, Animal, Drosophila Proteins, Prions, Prion Proteins
This work was supported by funds from the NC3Rs Project (Grant NC/K000462/1).
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/K000462/1)
External DOI: https://doi.org/10.1093/brain/awy183
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280007
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International