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Science 7 July 2006:
Vol. 313. no. 5783, pp. 94 - 97
DOI: 10.1126/science.1128635

Reports

Prion-Induced Amyloid Heart Disease with High Blood Infectivity in Transgenic Mice

Matthew J. Trifilo,1 Toshitaka Yajima,2 Yusu Gu,2 Nancy Dalton,2 Kirk L. Peterson,2 Richard E. Race,3 Kimberly Meade-White,3 John L. Portis,3 Eliezer Masliah,4 Kirk U. Knowlton,2* Bruce Chesebro,3* Michael B. A. Oldstone1*

We investigated extraneural manifestations in scrapie-infected transgenic mice expressing prion protein lacking the glycophosphatydylinositol membrane anchor. In the brain, blood, and heart, both abnormal protease-resistant prion protein (PrPres) and prion infectivity were readily detected by immunoblot and by inoculation into nontransgenic recipients. The titer of infectious scrapie in blood plasma exceeded 107 50% infectious doses per milliliter. The hearts of these transgenic mice contained PrPres-positive amyloid deposits that led to myocardial stiffness and cardiac disease.

1 Viral-Immunobiology Laboratory, Departments of Molecular and Integrative Neurosciences and Infectology, Scripps Research Institute, La Jolla, CA 92037, USA.
2 Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
3 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA.
4 Departments of Neurosciences and Pathology, University of California, San Diego, CA 92093, USA.

* To whom correspondence should be addressed. E-mail: mbaobo{at}scripps.edu (M.B.A.O.), bchesebro{at}niaid.nih.gov (B.C.), kknowlton{at}ucsd.edu (K.U.K.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)