NR AXNM
AU Green,K.M.; Castilla,J.; Seward,T.S.; Soto,C.; Telling,G.C.
TI Accelerated Sudies of Interspecies Prion Transmission Using Combined Transgenic and PMCA Technologies
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC2.7
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB
The threats to humans and livestock from interspecies prion transmission are difficult to assess because the factors controlling this process remain uncertain. The origin and potential for further interspecies transmission by cervid prions are of particular concern. Once thought to be confined to the endemic region of Northern Colorado and Southern Wyoming, chronic wasting disease (CWD) is a contagious prion disease of increasing geographic distribution, and is the only recognized prion disease of wild animals. Transgenic mouse models have been valuable for understanding the interplay between PrP primary structure and prion strains in determining interspecies prion transmission. The development of PMCA prompted us to explore the feasibility of accelerating these studies by combining in vitro prion amplification with transgenic approaches. Here we show using PMCA and Tg(CerPrP)1536 mice that PMCAamplified cervid prions retain the biological and biochemical properties of naturallyoccurring CWD prions. We also show that PMCA can be used to overcome the barrier to prion transmission that normally exists between rodents and cervids. We induced the production of novel RML-derived cervid prions by amplifying CerPrPc isolated
from Tg(CerPrP) mouse brains with RML following several rounds of PMCA amplification. Surprisingly, these RML-cervid prions had accelerated transmission properties in Tg(CerPrP)1536 mice compared to CWD and RML prions. The biochemical strain properties of the newly derived CerPrPsc were markedly different to CerPrPsc constituting CWD prions. In contrast, the production of similar RMLderived cervid prions required several hundred days in Tg(CerPrP) mice. Our studies demonstrate that the combination of transgenic and PMCA technologies is a powerful means of generating novel prion strains and for accelerating the study of interspecies prion transmission.
AD K.M. Green, University of Kentucky, Microbiology, Immunology, and Molecular Genetics, USA; J. Castilla, Scripps Research Institute, Department of Infectology, USA; T.S. Seward, G.C. Telling, University of Kentucky, Sanders Brown Center on Aging, USA; C. Soto, University of Texas Medical Branch, Department of Neurology, USA
SP englisch
PO Schottland