Synthetic Mammalian Prions

作者：Giuseppe Legname, Ilia V. Baskakov, Hoang-Oanh B. Nguyen, Detlev Riesner, Fred E. Cohen, Stephen J. DeArmond, Stanley Ben Prusiner · 发表于：Science · 年份：2004 · DOI：10.1126/science.1100195 · 被引用次数：1026 · 研究领域：Prion Diseases and Protein Misfolding、Neurological diseases and metabolism、Trace Elements in Health

Recombinant mouse prion protein (recMoPrP) produced in Escherichia coli was polymerized into amyloid fibrils that represent a subset of beta sheet-rich structures. Fibrils consisting of recMoPrP(89-230) were inoculated intracerebrally into transgenic (Tg) mice expressing MoPrP(89-231). The mice developed neurologic dysfunction between 380 and 660 days after inoculation. Brain extracts showed protease-resistant PrP by Western blotting; these extracts transmitted disease to wild-type FVB mice and Tg mice overexpressing PrP, with incubation times of 150 and 90 days, respectively. Neuropathological findings suggest that a novel prion strain was created. Our results provide compelling evidence that prions are infectious proteins.