Synthetic mammalian prions.
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.
Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA.
Giuseppe
G
Legname
Ilia V
IV
Baskakov
Hoang-Oanh B
HO
Nguyen
Detlev
D
Riesner
Fred E
FE
Cohen
Stephen J
SJ
DeArmond
Stanley B
SB
Prusiner
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001704:Biopolymers; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006031:Glycosylation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000473:pathology; D018620:PrPSc Proteins / Q000032:analysis / Q000378:metabolism; D017096:Prion Diseases / Q000209:etiology* / Q000473:pathology / Q000635:transmission; D011328:Prions / Q000008:administration & dosage / Q000096:biosynthesis / Q000737:chemistry / Q000472:pathogenicity*; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000737:chemistry; D013997:Time Factors; D014020:Tissue Extracts / Q000008:administration & dosage; D014617:Vacuoles / Q000473:pathology
D000682:Amyloid; D001704:Biopolymers; D018620:PrPSc Proteins; D011328:Prions; D011994:Recombinant Proteins; D014020:Tissue Extracts