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From: TSS ()
Subject: Passage of chronic wasting disease prion into transgenic mice expressing Rocky Mountain elk (Cervus elaphus nelsoni) PrPC
Date: November 16, 2006 at 1:08 pm PST

J Gen Virol 87 (2006), 3773-3780; DOI 10.1099/vir.0.82137-0

Passage of chronic wasting disease prion into transgenic mice expressing Rocky Mountain elk (Cervus elaphus nelsoni) PrPC

Giuseppe LaFauci1, Richard I. Carp1, Harry C. Meeker1, Xuemin Ye1,, Jae I. Kim1,, Michael Natelli1, Marisol Cedeno1, Robert B. Petersen2, Richard Kascsak1 and Richard Rubenstein1,

1 New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
2 Case Western Reserve University – Institute of Pathology, 2085 Adelbert Road, Cleveland, OH 44120, USA


Correspondence
Richard Rubenstein
Richard.rubenstein@downstate.edu

Chronic wasting disease (CWD) of elk (Cervus elaphus nelsoni) and mule deer (Odocoileus hemionus) is one of three naturally occurring forms of prion disease, the others being Creutzfeldt–Jakob disease in humans and scrapie in sheep. In the last few decades, CWD has spread among captive and free-ranging cervids in 13 US states, two Canadian provinces and recently in Korea. The origin of the CWD agent(s) in cervids is not known. This study describes the development of a transgenic mouse line (TgElk) homozygous for a transgene array encoding the elk prion protein (PrPC) and its use in propagating and simulating CWD in mice. Intracerebral injection of one mule deer and three elk CWD isolates into TgElk mice led to disease with incubation periods of 127 and 95 days, respectively. Upon secondary passage, the incubation time was reduced to 108 and 90 days, respectively. Upon passage into TgElk mice, CWD prions (PrPSc) maintained the characteristic Western blot profiles seen in CWD-affected mule deer and elk and produced histopathological modifications consistent with those observed in the natural disease. The short incubation time observed on passage from cervid to mouse with both mule deer and elk CWD brain homogenates and the demonstrated capacity of the animals to propagate (mouse to mouse) CWD agents make the TgElk line a valuable model to study CWD agents in cervid populations. In addition, these results with this new transgenic line suggest the intriguing hypothesis that there could be more than one strain of CWD agent in cervids.

Present address: Mount Sinai Medical Center, Department of Ophthalmology, 1 Gustave L. Levy Place, Box 1183, NY 10029, USA.

Present address: Case Western Reserve University – Institute of Pathology, 2085 Adelbert Road, Cleveland, OH 44120, USA.

Present address: SUNY Downstate Medical Center, Dept of Biochemistry, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.


http://vir.sgmjournals.org/cgi/content/abstract/87/12/3773

several other TSE studies in December issue ;

http://vir.sgmjournals.org/cgi/search?fulltext=PRION&sendit=Enter&volume=87&issue=12

TSS




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