NR AXIF
AU Asante,E.A.; Gowland,I.; Linehan,J.M.; Joiner,S.; Osiguwa,O.; Smidak,M.; Houghton,R.; Tomlinson,A.; Brandner,S.; Wadsworth,J.D.F.; Collinge,J.
TI Comparative Transmission Properties of P102L and E200K CJD Prions in Transgenic Mice
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.05
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Prion diseases are a group of rare neurodegenerative diseases that uniquely occur in sporadic, inherited and infectious forms. Pathogenic mutations in the human prion protein gene, designated PRNP, have been linked with inherited prion diseases. Inherited prion diseases are thought to be primarily genetic in nature with an autosomal-dominant pattern of inheritance. It is not yet clear whether all inherited prion diseases are transmissible by inoculation. To study the transmission properties of inherited prion diseases, we have generated a number of transgenic lines expressing varying levels of human prion protein with disease-associated PRNP mutations. Here we report on a comparative study of the transmission properties of prion proteins with two such mutations, leucine-102 and lysine-200. Transgenic mice homozygous for leucine-102 (methionine-129) or homozygous for lysine-200 (methionine-129), had quite different susceptibilities to the same isolates of sporadic CJD. However, leucine102 and lysine-200 transgenic mice were more readily susceptible to inherited prion disease P102L and E200K prions respectively. In addition, codon 129 mismatch between E200K inoculum and host PrP leads to a dramatic alteration of incubation periods. Finally, vCJD prions resulted in 100% subclinical infection and was accompanied by the formation of abundant florid plaques in both leucine-102 and lysine-200 mice, suggesting that PrP disease-associated mutations do not mitigate the propensity of vCJD to form florid plaques in human PrP methionine-129 homozygous experimental models.
AD E.A. Asante, I. Gowland, J.M. Linehan, S. Joiner, O. Osiguwa, M. Smidak, R. Houghton, A. Tomlinson, S. Brandner, J.D.F. Wadsworth, J. Collinge, Institute of Neurology, MRC Prion Unit, UK
SP englisch
PO Schottland