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De novo generation of a transmissible spongiform encephalopathy by mouse transgenesis.
UniversitätsSpital Zürich.
Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.ORCID iD: 0000-0002-5582-140X
Institut für Molekularbiologie und Biophysik, ETH Zürich.
UniversitätsSpital Zürich.
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2009 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 1, 304-309 p.Article in journal (Refereed) Published
Abstract [en]

Most transmissible spongiform encephalopathies arise either spontaneously or by infection. Mutations of PRNP, which encodes the prion protein, PrP, segregate with phenotypically similar diseases. Here we report that moderate overexpression in transgenic mice of mPrP(170N,174T), a mouse PrP with two point mutations that subtly affect the structure of its globular domain, causes a fully penetrant lethal spongiform encephalopathy with cerebral PrP plaques. This genetic disease was reproduced with 100% attack rate by intracerebral inoculation of brain homogenate to tga20 mice overexpressing WT PrP, and from the latter to WT mice, but not to PrP-deficient mice. Upon successive transmissions, the incubation periods decreased and PrP became more protease-resistant, indicating the presence of a strain barrier that was gradually overcome by repeated passaging. This shows that expression of a subtly altered prion protein, with known 3D structure, efficiently generates a prion disease.

Place, publisher, year, edition, pages
2009. Vol. 106, no 1, 304-309 p.
National Category
Natural Sciences
URN: urn:nbn:se:liu:diva-60075DOI: 10.1073/pnas.0810680105ISI: 000262263900056PubMedID: 19073920OAI: diva2:354942
Available from: 2010-10-05 Created: 2010-10-05 Last updated: 2014-04-08

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Nilsson, Peter
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