Publication
Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions
Journal Paper/Review - Apr 17, 1998
Shmerling D, Aguzzi A, Hangartner C, von Mering C, Cozzio Antonio, Flechsig E, Rülicke T, Götz J, Brandner S, Blättler T, Fischer M, Hegyi I, Weissmann C
Units
PubMed
Citation
Type
Journal
Publication Date
Issn Print
Pages
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.