NR AKVB
AU Shmerling,D.; Hegyi,I.; Fischer,M.; Blättler,T.; Brandner,S.; Götz,J.; Rülicke,T.; Flechsig,E.; Cozzio,A.; von Mering,C.; Hangartner,C.; Aguzzi,A.; Weissmann,C.
TI Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions
QU Cell 1998 Apr 17; 93(2): 203-14
PT journal article
AB 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.
MH Alleles; Animal; Ataxia/genetics/*pathology; Brain Chemistry; Cell Death; Cerebellum/chemistry/*pathology; Genes/physiology; Mice; Mice, Transgenic; Neurons/pathology; Phenotype; Prions/analysis/*genetics; RNA, Messenger/analysis; Scrapie/genetics/*pathology; *Sequence Deletion; Support, Non-U.S. Gov't; Time Factors
AD Institut für Molekularbiologie, Abteilung I, Universität Zürich, Switzerland.
SP englisch
PO USA