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A molecular switch controls interspeciesprion disease transmission in mice
University of California San Diego.
University Hospital of Zurich.ORCID iD: 0000-0002-5582-140X
University Hospital of Zurich.
University Hospital of Zurich.
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2010 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 120, 2590-2599 p.Article in journal (Refereed) Published
Abstract [en]

Transmissible spongiform encephalopathies are lethal neurodegenerative disorders that present with aggregated forms of the cellular prion protein (PrPC), which are known as PrPSc. Prions from different species vary considerably in their transmissibility to xenogeneic hosts. The variable transmission barriers depend on sequence differences between incoming PrPSc and host PrPC and additionally, on strain-dependent conformational properties of PrPSc. The β22 loop region within PrPC varies substantially between species, with its structure being influenced by the residue types in the 2 amino acid sequence positions 170 (most commonly S or N) and 174 (N or T). In this study, we inoculated prions from 5 different species into transgenic mice expressing either disordered-loop or rigid-loop PrPC variants. Similar β22 loop structures correlated with efficient transmission, whereas dissimilar loops correlated with strong transmission barriers. We then classified literature data on cross-species transmission according to the 170S/N polymorphism. Transmission barriers were generally low between species with the same amino acid residue in position 170 and high between those with different residues. These findings point to a triggering role of the local β22 loop structure for prion transmissibility between different species.

Place, publisher, year, edition, pages
American Society for Clinical Investigation , 2010. Vol. 120, 2590-2599 p.
National Category
Cell and Molecular Biology
URN: urn:nbn:se:liu:diva-73483DOI: 10.1172/JCI42051OAI: diva2:473028
Available from: 2012-01-04 Created: 2012-01-04 Last updated: 2014-04-08

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Nilsson, Peter
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