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MEDICAL SCIENCES
Kuru prions and sporadic Creutzfeldt–Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice

Jonathan D. F. Wadsworth, Susan Joiner, Jacqueline M. Linehan, Melanie Desbruslais, Katie Fox, Sharon Cooper, Sabrina Cronier, Emmanuel A. Asante, Simon Mead, Sebastian Brandner, Andrew F. Hill^*, and John Collinge

Medical Research Council Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom

Communicated by Charles Weissmann, The Scripps Research Institute, Jupiter, FL, January 10, 2008 (received for review October 10, 2007)

Abstract

Kuru provides our principal experience of an epidemic human prion disease and primarily affected the Fore linguistic group of the Eastern Highlands of Papua New Guinea. Kuru was transmitted by the practice of consuming dead relatives as a mark of respect and mourning (transumption). To date, detailed information of the prion strain type propagated in kuru has been lacking. Here, we directly compare the transmission properties of kuru prions with sporadic, iatrogenic, and variant Creutzfeldt–Jakob disease (CJD) prions in Prnp-null transgenic mice expressing human prion protein and in wild-type mice. Molecular and neuropathological data from these transmissions show that kuru prions are distinct from variant CJD and have transmission properties equivalent to those of classical (sporadic) CJD prions. These findings are consistent with the hypothesis that kuru originated from chance consumption of an individual with sporadic CJD.

variant CJD | transmissible spongiform encephalopathy | iatrogenic CJD

Author contributions: J.D.F.W., S.B., and J.C. designed research; J.D.F.W., S.J., J.M.L., M.D., K.F., S. Cooper, S. Cronier, E.A.A., S.B., and A.F.H. performed research; J.D.F.W., S.J., J.M.L., M.D., K.F., S. Cooper, E.A.A., S.M., S.B., A.F.H., and J.C. analyzed data; and J.D.F.W., S.M., A.F.H., and J.C. wrote the paper.

*Present address: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia.

Conflict of interest statement: J.C. is a director, and J.C., A.F.H., and J.D.F.W. are shareholders and consultants, of D-Gen Limited, an academic spin-out company working in the field of prion disease diagnosis, decontamination, and therapeutics. D-Gen markets the ICSM35 antibody used in this study.

To whom correspondence should be addressed. E-mail: j.collinge{at}prion.ucl.ac.uk

© 2008 by The National Academy of Sciences of the USA

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