Seminars Archive

Mouse synthetic prions

Abstract
We recently described the in vitro production of infectious prions from purified recombinant mouse (Mo) prion protein (PrP) residue 89 to 230. MoPrP(89-230) was refolded into highly b-sheet rich amyloid protein preparation and inoculated into transgenic (Tg) mice harboring the same sequence. At least two novel Mo synthetic prion strains were identified as judged by: i) incubation times, ii) conformational stability assay and iii) neuropathological changes (Legname et al. 2004; Legname et al. 2005). In another set of experiments, amyloid fibrils were produced using either truncated MoPrP(89-230) or full-length MoPrP(23-230). These preparations were injected into Tg mice expressing full-length MoPrP(23-231). Mice inoculated with either amyloid preparations developed prion disease at ª600 days. Two distinct strains were found to infect these Tg mice, one derived from the truncated and one from the full-length protein. In particular, MoPrP(23-230)-derived fibrils yielded a highly amyloidogenic strain as shown by immuno-histochemistry and thioflavin S positive stained plaques found in the brain of infected mice. Altogether that prions could be generated in vitro supports the hypothesis that the PrP alone is the sole infectious agent responsible for mammalian prion diseases. References: Legname G., Nguyen H.-O. B., Baskakov I. V., Cohen F. E., DeArmond S. J. and Prusiner S. B. (2005) Strain-specified characteristics of mouse synthetic prions. Proc. Natl. Acad. Sci. USA 102, 2168-2173. Legname G., Baskakov I. V., Nguyen H.-O. B., Riesner D., Cohen F. E., DeArmond S. J. and Prusiner S. B. (2004) Synthetic mammalian prions. Science 305, 673-676.