Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amyloid / chemistry
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Amyloid / metabolism
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Animals
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Biopolymers
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Brain / metabolism
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Brain / pathology
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Brain Chemistry
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Escherichia coli / genetics
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Female
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Glycosylation
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Male
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Mice
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Mice, Transgenic
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Plaque, Amyloid / pathology
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PrPSc Proteins / analysis
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PrPSc Proteins / metabolism
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Prion Diseases / etiology*
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Prion Diseases / pathology
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Prion Diseases / transmission
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Prions / administration & dosage
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Prions / biosynthesis
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Prions / chemistry
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Prions / pathogenicity*
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Protein Conformation
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Protein Folding
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Time Factors
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Tissue Extracts / administration & dosage
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Vacuoles / pathology
Substances
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Amyloid
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Biopolymers
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PrPSc Proteins
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Prions
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Recombinant Proteins
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Tissue Extracts