Recombinant prion protein induces a new transmissible prion disease in wild-type animals |
| |
Authors: | Natallia Makarava Gabor G Kovacs Olga Bocharova Regina Savtchenko Irina Alexeeva Herbert Budka Robert G Rohwer Ilia V Baskakov |
| |
Institution: | (1) Medical Biotechnology Center, University of Maryland Biotechnology Institute, 725 W. Lombard St., Baltimore, MD 21201, USA;(2) Institute of Neurology, Medical University of Vienna, AKH 4J, 1097 Vienna, Austria;(3) Medical Research Service, Veterans Affairs Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201, USA;(4) Department of Neurology, University of Maryland, Baltimore, MD 21201, USA;(5) Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, MD 21201, USA; |
| |
Abstract: | Prion disease is a neurodegenerative malady, which is believed to be transmitted via a prion protein in its abnormal conformation
(PrPSc). Previous studies have failed to demonstrate that prion disease could be induced in wild-type animals using recombinant
prion protein (rPrP) produced in Escherichia coli. Here, we report that prion infectivity was generated in Syrian hamsters after inoculating full-length rPrP that had been
converted into the cross-β-sheet amyloid form and subjected to annealing. Serial transmission gave rise to a disease phenotype
with highly unique clinical and neuropathological features. Among them were the deposition of large PrPSc plaques in subpial and subependymal areas in brain and spinal cord, very minor lesioning of the hippocampus and cerebellum,
and a very slow progression of disease after onset of clinical signs despite the accumulation of large amounts of PrPSc in the brain. The length of the clinical duration is more typical of human and large animal prion diseases, than those of
rodents. Our studies establish that transmissible prion disease can be induced in wild-type animals by inoculation of rPrP
and introduce a valuable new model of prion diseases. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|