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From: TSS ()
Subject: Transmission of Elk and Deer Prions to Transgenic Mice
Date: September 1, 2006 at 1:07 pm PST

Journal of Virology, September 2006, p. 9104-9114, Vol. 80, No. 18
0022-538X/06/$08.00+0 doi:10.1128/JVI.00098-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transmission of Elk and Deer Prions to Transgenic Mice

Gültekin Tamgüney,1 Kurt Giles,1,2 Essia Bouzamondo-Bernstein,3 Patrick J. Bosque,1,2, Michael W. Miller,4 Jiri Safar,1,2 Stephen J. DeArmond,1,3 and Stanley B. Prusiner1,2,5*
Institute for Neurodegenerative Diseases,1 Departments of Neurology,2 Pathology,3 Biochemistry and Biophysics, University of California, San Francisco, California,5 Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, Colorado4

Received 13 January 2006/ Accepted 21 June 2006

Chronic wasting disease (CWD) is a fatal prion disease in deer and elk. Unique among the prion diseases, it is transmitted among captive and free-ranging animals. To facilitate studies of the biology of CWD prions, we generated five lines of transgenic (Tg) mice expressing prion protein (PrP) from Rocky Mountain elk (Cervus elaphus nelsoni), denoted Tg(ElkPrP), and two lines of Tg mice expressing PrP common to white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus), denoted Tg(DePrP). None of the Tg(ElkPrP) or Tg(DePrP) mice exhibited spontaneous neurologic dysfunction at more than 600 days of age. Brain samples from CWD-positive elk, white-tailed deer, and mule deer produced disease in Tg(ElkPrP) mice between 180 and 200 days after inoculation and in Tg(DePrP) mice between 300 and 400 days. One of eight cervid brain inocula transmitted disease to Tg(MoPrP)4053 mice overexpressing wild-type mouse PrP-A in 540 days. Neuropathologic analysis revealed abundant PrP amyloid plaques in the brains of ill mice. Brain homogenates from symptomatic Tg(ElkPrP) mice produced disease in 120 to 190 days in Tg(ElkPrP) mice. In contrast to the Tg(ElkPrP) and Tg(DePrP) mice, Tg mice overexpressing human, bovine, or ovine PrP did not develop prion disease after inoculation with CWD prions from among nine different isolates after >500 days. These findings suggest that CWD prions from elk, mule deer, and white-tailed deer can be readily transmitted among these three cervid species.

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* Corresponding author. Mailing address: Institute for Neurodegenerative Diseases, 513 Parnassus Ave., HSE-774, University of California, San Francisco, CA 94143-0518. Phone: (415) 476-4482. Fax: (415) 476-8386. E-mail: stanley@ind.ucsf.edu .

Supplemental material for this article may be found at http://jvi.asm.org/.

Present address: Department of Neurology, University of Colorado Health Sciences Center, Denver, CO 80262.

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Journal of Virology, September 2006, p. 9104-9114, Vol. 80, No. 18
0022-538X/06/$08.00+0 doi:10.1128/JVI.00098-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.


http://jvi.asm.org/cgi/content/abstract/80/18/9104



TSS




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