Abstract
ACCUMULATION of the prion protein PrPSc, a pathological and protease-resistant isoform of the normal host protein PrPc, is a feature of prion disease such as scrapie1,2. It is still unknown whether scrapie pathology comes about by neurotoxicity of PrPSc, acute depletion of PrPc, or some other mechanism. Here we investigate this question by grafting neural tissue overexpressing PrPc into the brain of PrP-deficient mice which are scrapie-resistant and do not propagate infectivity3–5. After intracerebral inoculation with scrapie prions, the grafts accumulated high levels of PrPSc and infectivity and developed the severe histopathological changes characteristic of scrapie. Moreover, substantial amounts of graft-derived PrPSc migrated into the host brain. Even 16 months after inoculation no pathological changes were seen in PrP-deficient tissue, not even in the immediate vicinity of the grafts. Therefore, in addition to being resistant to scrapie infection, brain tissue devoid of PrPc is not damaged by exogenous PrPSc.
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References
Prusiner, S. B. A. Rev. Microbiol. 48, 655–686 (1994).
Weissmann, C. Trends Cell Biol. 4, 10–14 (1994).
Büeler, H. R. et al. Nature 356, 577–582 (1992).
Büeler, H. R. et al. Cell 73, 1339–1347 (1993).
Sailer, A., Büeler, H., Fischer, M., Aguzzi, A. & Weissmann, C. Cell 77, 967–968 (1994).
Fischer, M. et al. EMBO J. (in the press).
Taraboulos, A. et al. Proc. natn. Acad. Sci. U.S.A. 89, 7620–7624 (1992).
Isenmann, S., Brandner, S., Sure, U. & Aguzzi, A. Neuropathol. appl. Neurobiol. (in the press).
Jeffrey, M. et al. Neurosci. Lett. 174, 39–42 (1994).
Manson, J. C. et al. Molec. Neurobiol. 8, 121–127 (1994).
Jeffrey, M. et al. Brain Res. 656, 329–343 (1994).
Forloni, G. et al. Nature 362, 543–546 (1993).
Müller, W. E. et al. Eur. J. Pharmac. 246, 261–267 (1993).
Collinge, J. et al. Lancet 336, 7–9 (1990).
Hayward, P. A., Bell, J. E. & Ironside, J. W. Neuropath. appl. Neurobiol. 20, 375–383 (1994).
Shyng, S. L., Huber, M. T. & Harris, D. A. J. biol. Chem. 268, 15922–15928 (1993).
Büeler, H. et al. Molec. Med. 1, 19–30 (1994).
Manson, J. C., Clarke, A. R., McBride, P. A., McConnell, I. & Hope, J. Neurodegeneration 3, 331–340 (1994).
Collinge, J. et al. Lancet 346, 569–570 (1995).
Reed, J. & Muench, H. Am. J. Hyg. 27, 493–497 (1938).
Prusiner, S. B. et al. Ann. Neurol. 11, 353–358 (1982).
Farquhar, C. F., Somerville, R. A. & Ritchie, L. A. J. virol. Meth. 24, 215–221 (1989).
Schaeren-Wiemers, N. & Gerfin-Moser, A. Histochemistry 100, 431–440 (1993).
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Brandner, S., Isenmann, S., Raeber, A. et al. Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379, 339–343 (1996). https://doi.org/10.1038/379339a0
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DOI: https://doi.org/10.1038/379339a0
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