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Prion protein devoid of the octapeptide repeat region restores susceptibility to scrapie in PrP knockout mice


Flechsig, E; Shmerling, D; Hegyi, I; Raeber, A J; Fischer, M B; Cozzio, A; von Mering, C; Aguzzi, A; Weissmann, C (2000). Prion protein devoid of the octapeptide repeat region restores susceptibility to scrapie in PrP knockout mice. Neuron, 27(2):399-408.

Abstract

Mice devoid of PrP are resistant to scrapie and fail to replicate the agent. Introduction of transgenes expressing PrP into such mice restores susceptibility to scrapie. We find that truncated PrP devoid of the five copper binding octarepeats still sustains scrapie infection; however, incubation times are longer and prion titers and protease-resistant PrP are about 30-fold lower than in wild-type mice. Surprisingly, brains of terminally ill animals show no histopathology typical for scrapie. However, in the spinal cord, infectivity, gliosis, and motor neuron loss are as in scrapie-infected wild-type controls. Thus, while the region comprising the octarepeats is not essential for mediating pathogenesis and prion replication, it modulates the extent of these events and of disease presentation.

Mice devoid of PrP are resistant to scrapie and fail to replicate the agent. Introduction of transgenes expressing PrP into such mice restores susceptibility to scrapie. We find that truncated PrP devoid of the five copper binding octarepeats still sustains scrapie infection; however, incubation times are longer and prion titers and protease-resistant PrP are about 30-fold lower than in wild-type mice. Surprisingly, brains of terminally ill animals show no histopathology typical for scrapie. However, in the spinal cord, infectivity, gliosis, and motor neuron loss are as in scrapie-infected wild-type controls. Thus, while the region comprising the octarepeats is not essential for mediating pathogenesis and prion replication, it modulates the extent of these events and of disease presentation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 August 2000
Deposited On:11 Feb 2008 12:26
Last Modified:05 Apr 2016 12:21
Publisher:Elsevier
ISSN:0896-6273
Publisher DOI:10.1016/S0896-6273(00)00046-5
Related URLs:http://linkinghub.elsevier.com/retrieve/pii/S0896-6273(00)00046-5
PubMed ID:10985358
Permanent URL: http://doi.org/10.5167/uzh-1925

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