NR ATRO
AU Sigurdson,C.J.; Heikenwälder,M.; Manco,G.; Hornemann,S.; Liberski,P.; Pahnke,J.; Baumann,F.; Miele,G.; Wüthrich,K.; Aguzzi,A.
TI Spongiform encephalopathy and prion plaque generation by mouse transgenesis
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Structure of PrP and molecular determinants of infectivity STRCT-30
PT Konferenz-Poster
AB
Chronic wasting disease (CWD) is a naturally-occurring, geographically widespread prion disease in captive and free-ranging North American deer and elk, with unknown potential as a human health threat. The elk PrPc structure contains 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 with 100% penetrance characterized by vacuolar change, gliosis, microglial activation, and PrP plaques in the brain, similar to deer with CWD or patients with variant CJD or Gerstmann-Sträussler-Scheinker syndrome (GSS), and typical of a transmissible spongiform encephalopathy.
1. Gossert, A.D., et al., Prion protein NMR structures of elk and of mouse/elk hybrids. Proc Natl Acad Sci U S A, 2005. 102(3): p. 646-50
AD C.Sigurdson, M.Heikenwälder, G.Manco, J.Pahnke, F.Baumann, G.Miele, 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
SP englisch
PO Deutschland