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Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions.


Shmerling, D; Hegyi, I; Fischer, M B; Blättler, T; Brandner, S; Götz, J; Rülicke, T; Flechsig, E; Cozzio, A; von Mering, C; Hangartner, C; Aguzzi, A; Weissmann, C (1998). Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell, 93(2):203-214.

Abstract

The physiological role of prion protein (PrP) remains unknown. Mice devoid of PrP develop normally but are resistant to scrapie; introduction of a PrP transgene restores susceptibility to the disease. To identify the regions of PrP necessary for this activity, we prepared PrP knockout mice expressing PrPs with amino-proximal deletions. Surprisingly, PrP lacking residues 32-121 or 32-134, but not with shorter deletions, caused severe ataxia and neuronal death limited to the granular layer of the cerebellum as early as 1-3 months after birth. The defect was completely abolished by introducing one copy of a wild-type PrP gene. We speculate that these truncated PrPs may be nonfunctional and compete with some other molecule with a PrP-like function for a common ligand.

The physiological role of prion protein (PrP) remains unknown. Mice devoid of PrP develop normally but are resistant to scrapie; introduction of a PrP transgene restores susceptibility to the disease. To identify the regions of PrP necessary for this activity, we prepared PrP knockout mice expressing PrPs with amino-proximal deletions. Surprisingly, PrP lacking residues 32-121 or 32-134, but not with shorter deletions, caused severe ataxia and neuronal death limited to the granular layer of the cerebellum as early as 1-3 months after birth. The defect was completely abolished by introducing one copy of a wild-type PrP gene. We speculate that these truncated PrPs may be nonfunctional and compete with some other molecule with a PrP-like function for a common ligand.

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Additional indexing

Item Type:Journal Article, refereed
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:17 April 1998
Deposited On:11 Feb 2008 12:25
Last Modified:05 Apr 2016 12:20
Publisher:Elsevier
ISSN:0092-8674
Publisher DOI:10.1016/S0092-8674(00)81572-X
Related URLs:http://linkinghub.elsevier.com/retrieve/pii/S0092-8674(00)81572-X
PubMed ID:9568713
Permanent URL: http://doi.org/10.5167/uzh-1841

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