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Variant prion protein causes infection but no symptoms

Abnormal prion proteins are little understood disease agents involved in causing horrific brain-wasting diseases such as Creutzfeldt-Jacob disease in people, mad cow disease in cattle and chronic wasting disease in deer and elk. Now, new research suggests that a variant form of abnormal prion protein--one lacking an "anchor" into the cell membrane--may be unable to signal cells to start the lethal disease process, according to scientists at the Rocky Mountain Laboratories (RML), part of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health.

"This work provides novel insights into how prion and other neurodegenerative diseases develop and it provides tantalizing clues as to how we might delay or even prevent such diseases by preventing certain cellular interactions," notes NIAID Director Anthony S. Fauci, M.D. A paper describing the research was released online today by the journal Science. RML virologist Bruce Chesebro, M.D., directed the project. Other key co-authors from the Hamilton, MT, RML laboratory include Richard Race, D.V.M., and Gerald Baron, Ph.D. Their collaborators included Michael Oldstone, M.D., and Matthew Trifilo, Ph.D., of The Scripps Research Institute in La Jolla, CA, and Eliezer Masliah, M.D., of the University of California, San Diego (UCSD).

Drawing on experimental concepts first developed at RML a decade ago, the research team exposed two groups of 6-week-old mice to different strains of the agent that causes scrapie, a brain-wasting disease of sheep. Within 150 days of being inoculated with the natural form of scrapie prion protein, all 70 mice in the control group showed visible signs of infection: twitching, emaciation and poor coordination. In contrast, the scientists observed 128 transgenic mice--those engineered to produce prion protein without a glycophosphoinositol (GPI) cell membrane anchor--for 500 to 600 days and saw no signs of scrapie disease. Subsequent electron mic
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Source:NIH


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