NR ARRH
AU Legname,G.; Nguyen,H.O.B.; Baskakov,I.V.; Cohen,F.E.; DeArmond,S.J.; Prusiner,S.B.
TI Strain-specified characteristics of mouse synthetic prions
QU Proceedings of the National Academy of Sciences of the United States of America 2005 Feb 8; 102(6): 2168-73
IA http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=548557
PT journal article
AB Synthetic prions were produced in our laboratory by using recombinant mouse prion protein (MoPrP) composed of residues 89-230. The first mouse synthetic prion strain (MoSP1) was inoculated into transgenic (Tg) 9949 mice expressing N-terminally truncated MoPrP(Delta23-88) and WT FVB mice expressing full-length MoPrP. On first and second passage in Tg9949 mice, MoSP1 prions caused disease in 516 +/- 27 and 258 +/- 25 days, respectively; numerous, large vacuoles were found in the brainstem and gray matter of the cerebellum. MoSP1 prions passaged in Tg9949 mice were inoculated into FVB mice; on first and second passage, the FVB mice exhibited incubation times of 154 +/- 4 and 130 +/- 3 days, respectively. In FVB mice, vacuolation was less intense but more widely distributed, with numerous lesions in the hippocampus and cerebellar white matter. This constellation of widespread neuropatho-logic changes was similar to that found in FVB mice inoculated with Rocky Mountain Laboratory (RML) prions, a strain derived from a sheep with scrapie. Conformational stability studies showed that the half-maximal GdnHCl (Gdn1/2) concentration for denaturation of MoSP1 prions passaged in Tg9949 mice was approximately 4.2 M; passage in FVB mice reduced the Gdn1/2 value to approximately 1.7 M. RML prions passaged in either Tg9949 or FVB mice exhibited Gdn1/2 values of approximately 1.8 M. The incubation times, neuropathological lesion profiles, and Gdn1/2 values indicate that MoSP1 prions differ from RML and many other prion strains derived from sheep with scrapie and cattle with bovine spongiform encephalopathy.
MH Animals; Brain/metabolism/pathology; Cattle; Humans; Mice; *Mice, Transgenic; Peptide Fragments/chemistry/genetics/metabolism; *PrPsc Proteins/chemistry/genetics/metabolism; *Prions/chemical synthesis/chemistry/genetics/metabolism; Protein Conformation; Recombinant Proteins/genetics/*metabolism; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
AD Institute for Neurodegenerative Diseases , University of California, San Francisco, CA 94143, USA
SP englisch
PO USA