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From: TSS ()
Subject: Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Models
Date: September 1, 2005 at 2:20 pm PST

The Journal of Neuroscience, August 31, 2005, 25(35):7944-7949; doi:10.1523/JNEUROSCI.2467-05.2005

Neurobiology of Disease
Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Models

Qingzhong Kong,1 Shenghai Huang,1 Wenquan Zou,1 Difernando Vanegas,1 Meiling Wang,1 Di Wu,1 Jue Yuan,1 Mengjie Zheng,1 Hua Bai,1 Huayun Deng,2 Ken Chen,3 Allen L. Jenny,4 Katherine O'Rourke,5 Ermias D. Belay,6 Lawrence B. Schonberger,6 Robert B. Petersen,1 Man-Sun Sy,1 Shu G. Chen,1 and Pierluigi Gambetti1

Departments of 1Pathology and 2Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106, 3Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, 4National Veterinary Services Laboratories, United States Department of Agriculture, Ames, Iowa 50010, 5Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman, Washington 99164, and 6Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333

Chronic wasting disease (CWD), a prion disease affecting free-ranging and captive cervids (deer and elk), is widespread in the United States and parts of Canada. The large cervid population, the popularity of venison consumption, and the apparent spread of the CWD epidemic are likely resulting in increased human exposure to CWD in the United States. Whether CWD is transmissible to humans, as has been shown for bovine spongiform encephalopathy (the prion disease of cattle), is unknown. We generated transgenic mice expressing the elk or human prion protein (PrP) in a PrP-null background. After intracerebral inoculation with elk CWD prion, two lines of "humanized" transgenic mice that are susceptible to human prions failed to develop the hallmarks of prion diseases after >657 and >756 d, respectively, whereas the "cervidized" transgenic mice became infected after 118–142 d. These data indicate that there is a substantial species barrier for transmission of elk CWD to humans.

Key words: chronic wasting disease; CWD; transmissibility to humans; transgenic mice; prion; cervids; deer; elk; species barrier


Received June 16, 2005; revised July 18, 2005; accepted July 19, 2005.


Prion transmission in transgenic mice

Prion Inoculum Mice PrP (Level) Mean incubation time Transmission Rate

CWD (elk 1) Tg12 Elk PrP-132M (2x) 118+-20 days 13/14

CWD (elk 2) Tg12 Elk PrP-132M (2x) 142+-18 days 7/7

CWD (Tg12) Tg12 Elk PrP-132M (2x) 125+-8 days 5/5

sCJDMM1 Tg40 HuPrP-129M (1x) 263+-38 days 9/10

sCJDMM1 Tg1 HuPrP-129M (2x) 226+-13 days 7/7

CWD (elk 1/2) Tg40 HuPrP-129M (1x) >710 days 0/29

CWD (elk 1/2) Tg1 HuPrP-129M (2x) >611 days 0/22

source NPDPSC 2004-2005, NO URL.

IT will be very interesting to see what the 'second' round transmission studies will produce. ...TSS

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