NR AWNP
AU Sigurdson,C.J.; Heikenwälder,M.; Manco,G.; Hornemann,S.; Nilsson,P.; Liberski,P.; Ott,D.; Rülicke,T.; Pahnke,J.; Baumann,F.; Miele,G.; Stitz,L.; Schwarz,P.; Wüthrich,K.; Aguzzi,A.
TI Elk-like prion protein triggers spontaneous spongiform encephalopathy with florid plaques in mice
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions S-21
PT Konferenz-Poster
AB Chronic wasting disease (CWD) is a geographically widespread, naturally occurring prion disease of wild and captive North American cervids. The origin of CWD is unknown. Here we investigated an unusual structural feature of the elk PrPc, a well-defined loop connecting the second strand of the beta sheet with alpha helix 2 (amino acids 165-175) which is rigidified by two local hydrogen bond networks. These hydrogen bond networks are absent from mouse PrPc [1]. We have expressed a PrPc mutant in transgenic mice that mimics the elk "rigid loop" (RL). These transgenic mice develop a spontaneous neurologic disease characterized by vacuolar change, gliosis, microglial activation, and PrP plaques in the brain, similar to deer with CWD or patients with variant CJD and typical of a transmissible spongiform encephalopathy. Based on this unusual rigid structural feature of the elk PrP, it is tempting to speculate that the isolated geographic foci of CWD outbreaks across the U.S. and Canada may be due to increased risk for a sporadic disease that can then spread horizontally.
AD C. Sigurdson, M. Heikenwälder, G. Manco, P. Nilsson, J. Pahnke, F. Baumann, G. Miele, P. Schwarz, A. Aguzzi: Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland; S. Hornemann, K. Wüthrich: Institute of Molecular Biology and Biophysics, Eidgenössischen Technischen Hochschule, CH-8093 Zürich, Switzerland; P. Liberski: Medical University of Lodz, Al. Kosciuszki St. 4, PL 90-419 Lodz, Poland; T. Rülicke: Institute for Laboratory Animals, Veterinärmedizische Universitäat Wien, Veterinärplatz 1, 11210 Wien; L. Stitz: Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health,Institute of Immunology, Paul-Ehrlich-Strasse 28, 72076 Tübingen,Germany; D. Ott: nicht angegeben
SP englisch
PO Italien