Publication

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

Journal Paper/Review - Apr 17, 1998

Units
PubMed

Citation
Shmerling D, Aguzzi A, Hangartner C, von Mering C, Cozzio A, Flechsig E, Rülicke T, Götz J, Brandner S, Blättler T, Fischer M, Hegyi I, Weissmann C. Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Cell 1998; 93:203-14.
Type
Journal Paper/Review (English)
Journal
Cell 1998; 93
Publication Date
Apr 17, 1998
Issn Print
0092-8674
Pages
203-14
Brief description/objective

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.