Divergent prion strain evolution driven by PrPC expression level in transgenic mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01-23

AUTHORS

Annick Le Dur, Thanh Lan Laï, Marie-George Stinnakre, Aude Laisné, Nathalie Chenais, Sabine Rakotobe, Bruno Passet, Fabienne Reine, Solange Soulier, Laetitia Herzog, Gaëlle Tilly, Human Rézaei, Vincent Béringue, Jean-Luc Vilotte, Hubert Laude

ABSTRACT

Prions induce a fatal neurodegenerative disease in infected host brain based on the refolding and aggregation of the host-encoded prion protein PrPC into PrPSc. Structurally distinct PrPSc conformers can give rise to multiple prion strains. Constrained interactions between PrPC and different PrPSc strains can in turn lead to certain PrPSc (sub)populations being selected for cross-species transmission, or even produce mutation-like events. By contrast, prion strains are generally conserved when transmitted within the same species, or to transgenic mice expressing homologous PrPC. Here, we compare the strain properties of a representative sheep scrapie isolate transmitted to a panel of transgenic mouse lines expressing varying levels of homologous PrPC. While breeding true in mice expressing PrPC at near physiological levels, scrapie prions evolve consistently towards different strain components in mice beyond a certain threshold of PrPC overexpression. Our results support the view that PrPC gene dosage can influence prion evolution on homotypic transmission. More... »

PAGES

14170

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms14170

    DOI

    http://dx.doi.org/10.1038/ncomms14170

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1074204309

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28112164


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