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From: TSS ()
Subject: Resistance to CWD in Transgenic Mice Expressing a Naturally Occurring Allelic Variant of Deer Prion Protein
Date: April 12, 2007 at 9:17 am PST

Resistance to Chronic Wasting Disease in Transgenic Mice Expressing a Naturally Occurring Allelic Variant of Deer Prion Protein

Kimberly Meade-White,1 Brent Race,1 Matthew Trifilo,2 Alex Bossers,3 Cynthia Favara,1 Rachel Lacasse,1 Michael Miller,4 Elizabeth Williams,5 Michael Oldstone,2 Richard Race,1 and Bruce Chesebro1*

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, Hamilton, Montana 59840,1 Viral-Immunobiology Laboratory, Departments of Molecular and Integrative Neurosciences and Infectology, Scripps Research Institute, La Jolla, California,2 Central Institute for Animal Disease Control, Department of Bacteriology and TSEs, P.O. Box 2004, 8203 AA Lelystad, The Netherlands,3 Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, Colorado 80526-2097,4 Department of Veterinary Sciences, University of Wyoming, Laramie, Wyoming 820705

Received 14 December 2006/ Accepted 14 February 2007

Prion protein (PrP) is a required factor for susceptibility to transmissible spongiform encephalopathy or prion diseases. In transgenic mice, expression of prion protein (PrP) from another species often confers susceptibility to prion disease from that donor species. For example, expression of deer or elk PrP in transgenic mice has induced susceptibility to chronic wasting disease (CWD), the prion disease of cervids. In the current experiments, transgenic mice expressing two naturally occurring allelic variants of deer PrP with either glycine (G) or serine (S) at residue 96 were found to differ in susceptibility to CWD infection. G96 mice were highly susceptible to infection, and disease appeared starting as early as 160 days postinfection. In contrast, S96 mice showed no evidence of disease or generation of disease-associated protease-resistant PrP (PrPres) over a 600-day period. At the time of clinical disease, G96 mice showed typical vacuolar pathology and deposition of PrPres in many brain regions, and in some individuals, extensive neuronal loss and apoptosis were noted in the hippocampus and cerebellum. Extraneural accumulation of PrPres was also noted in spleen and intestinal tissue of clinically ill G96 mice. These results demonstrate the importance of deer PrP polymorphisms in susceptibility to CWD infection. Furthermore, this deer PrP transgenic model is the first to demonstrate extraneural accumulation of PrPres in spleen and intestinal tissue and thus may prove useful in studies of CWD pathogenesis and transmission by oral or other natural routes of infection.

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* Corresponding author. Mailing address: Rocky Mountain Laboratories, 903 South Fourth St., Hamilton, MT 59840. Phone: (406) 363-9354. Fax: (406) 363-9289. E-mail: bchesebro@nih.gov

Published ahead of print on 21 February 2007.

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Journal of Virology, May 2007, p. 4533-4539, Vol. 81, No. 9
0022-538X/07/$08.00+0 doi:10.1128/JVI.02762-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.


http://jvi.asm.org/cgi/content/abstract/81/9/4533?ct


TSS



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