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Science 30 July 2004:
Vol. 305. no. 5684, pp. 673 - 676
DOI: 10.1126/science.1100195
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Reports

Synthetic Mammalian Prions

Giuseppe Legname,1,2* Ilia V. Baskakov,1,2*{dagger} Hoang-Oanh B. Nguyen,1 Detlev Riesner,6 Fred E. Cohen,1,3,4 Stephen J. DeArmond,1,5 Stanley B. Prusiner1,2,4{ddagger}

Recombinant mouse prion protein (recMoPrP) produced in Escherichia coli was polymerized into amyloid fibrils that represent a subset of ß 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.

1 Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA.
2 Department of Neurology, University of California, San Francisco, CA 94143, USA.
3 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
4 Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
5 Department of Pathology, University of California, San Francisco, CA 94143, USA.
6 Institut für Physikalische Biologie, Heinrich-Heine-Universität, 40225 Düsseldorf, Germany.


* These two authors contributed equally to this work.

{dagger} Present address: Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA.

{ddagger} To whom correspondence should be addressed. E-mail: stanley{at}itsa.ucsf.edu

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Journal Watch Infectious Diseases 2004, 9
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Protein-only prions.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)