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Journal of Virology, February 2001, p. 1408-1413, Vol. 75, No. 3
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.3.1408-1413.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification of Two Prion Protein Regions That Modify Scrapie Incubation Time

Surachai Supattapone,1,2 Tamaki Muramoto,2,dagger Giuseppe Legname,1,2 Ingrid Mehlhorn,2,Dagger Fred E. Cohen,1,3,4,5 Stephen J. DeArmond,1,6 Stanley B. Prusiner,1,2,5 and Michael R. Scott1,2,*

Institute for Neurodegenerative Diseases1 and Departments of Neurology,2 Medicine,3 Pharmaceutical Chemistry,4 Biochemistry and Biophysics,5 and Pathology,6 University of California, San Francisco, California 94143

Received 8 August 2000/Accepted 23 October 2000

A series of prion transmission experiments was performed in transgenic (Tg) mice expressing either wild-type, chimeric, or truncated prion protein (PrP) molecules. Following inoculation with Rocky Mountain Laboratory (RML) murine prions, scrapie incubation times for Tg(MoPrP)4053, Tg(MHM2)294/Prnp0/0, and Tg(MoPrP,Delta 23-88)9949/Prnp0/0 mice were ~50, 120, and 160 days, respectively. Similar scrapie incubation times were obtained after inoculation of these lines of Tg mice with either MHM2(MHM2(RML)) or MoPrP(Delta 23-88)(RML) prions, excluding the possibility that sequence-dependent transmission barriers could account for the observed differences. Tg(MHM2)294/Prnp0/0 mice displayed prolonged scrapie incubation times with four different strains of murine prions. These data provide evidence that the N terminus of MoPrP and the chimeric region of MHM2 PrP (residues 108 through 111) both influence the inherent efficiency of prion propagation.


* Corresponding author. Mailing address: Institute for Neurodegenerative Diseases, Box 0518, University of California, San Francisco, CA 94143-0518. Phone: (415) 476-4482. Fax: (415) 476-8386.

dagger Present address: Department of Neurological Science, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan 980-8575.

Dagger Present address: Montclair Group, Tal Biosciences, Alameda, CA 94501.


Journal of Virology, February 2001, p. 1408-1413, Vol. 75, No. 3
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.3.1408-1413.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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