liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Spongiform Encephalopathy in Transgenic Mice Expressing a Point Mutation in the beta 2-alpha 2 Loop of the Prion Protein
University of California San Diego.
University of California San Diego.
University of California San Diego.
University of California San Diego.
Show others and affiliations
2011 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 31, no 39, 13840-13847 p.Article in journal (Refereed) Published
Abstract [en]

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases attributed to misfolding of the cellular prion protein, PrP(C), into a beta-sheet-rich, aggregated isoform, PrP(Sc). We previously found that expression of mouse PrP with the two amino acid substitutions S170N and N174T, which result in high structural order of the beta 2-alpha 2 loop in the NMR structure at pH 4.5 and 20 C, caused transmissible de novo prion disease in transgenic mice. Here we report that expression of mouse PrP with the single-residue substitution D167S, which also results in a structurally well ordered beta 2-alpha 2 loop at 20 degrees C, elicits spontaneous PrP aggregation in vivo. Transgenic mice expressing PrP(D167S) developed a progressive encephalopathy characterized by abundant PrP plaque formation, spongiform change, and gliosis. These results add to the evidence that the beta 2-alpha 2 loop has an important role in intermolecular interactions, including that it may be a key determinant of prion protein aggregation.

Place, publisher, year, edition, pages
Society for Neuroscience , 2011. Vol. 31, no 39, 13840-13847 p.
National Category
Engineering and Technology
URN: urn:nbn:se:liu:diva-71550DOI: 10.1523/JNEUROSCI.3504-11.2011ISI: 000295363800016OAI: diva2:450528

Funding Agencies|National Institutes of Health| NS055116 NS069566 U54AI065359 |U.S. National Prion Research Program||European Union||Swiss National Science Foundation||Novartis Research Foundation||National Competence Centers for Research on Neural Plasticity and Repair and on Structural Biology||ETH Zurich||European Research Council||

Available from: 2011-10-21 Created: 2011-10-21 Last updated: 2015-05-28

Open Access in DiVA

fulltext(2368 kB)310 downloads
File information
File name FULLTEXT01.pdfFile size 2368 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Nilsson, Peter
By organisation
ChemistryFaculty of Science & Engineering
In the same journal
Journal of Neuroscience
Engineering and Technology

Search outside of DiVA

GoogleGoogle Scholar
Total: 310 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 79 hits
ReferencesLink to record
Permanent link

Direct link