title: Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions.
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.
authors.affiliation: Institut für Molekularbiologie, Abteilung I, Universität Zürich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Shmerling
authors.forename: I
authors.initials: I
authors.lastname: Hegyi
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.forename: T
authors.initials: T
authors.lastname: Blättler
authors.forename: S
authors.initials: S
authors.lastname: Brandner
authors.forename: J
authors.initials: J
authors.lastname: Götz
authors.forename: T
authors.initials: T
authors.lastname: Rülicke
authors.forename: E
authors.initials: E
authors.lastname: Flechsig
authors.forename: A
authors.initials: A
authors.lastname: Cozzio
authors.forename: C
authors.initials: C
authors.lastname: von Mering
authors.forename: C
authors.initials: C
authors.lastname: Hangartner
authors.forename: A
authors.initials: A
authors.lastname: Aguzzi
authors.forename: C
authors.initials: C
authors.lastname: Weissmann
mesh_terms: D000483:Alleles; D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000473:pathology*; D001923:Brain Chemistry; D016923:Cell Death; D002531:Cerebellum / Q000737:chemistry / Q000473:pathology*; D005796:Genes / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology; D010641:Phenotype; D011328:Prions / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012608:Scrapie / Q000235:genetics / Q000473:pathology*; D017384:Sequence Deletion; D013997:Time Factors
chemical_list: D011328:Prions; D012333:RNA, Messenger