title: Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain.
abstract: PrP knockout mice in which only the open reading frame was disrupted ('Zürich I') remained healthy. However, more extensive deletions resulted in ataxia, Purkinje cell loss and ectopic expression in brain of Doppel (Dpl), encoded by the downstream gene, PRND: A new PrP knockout line, 'Zürich II', with a 2.9 kb PRNP: deletion, developed this phenotype at approximately 10 months (50% morbidity). A single PRNP: allele abolished the syndrome. Compound Zürich I/Zürich II heterozygotes had half the Dpl of Zürich II mice and developed symptoms 6 months later. Zürich II mice transgenic for a PRND:-containing cosmid expressed Dpl at twice the level and became ataxic approximately 5 months earlier. Thus, Dpl levels in brain and onset of the ataxic syndrome are inversely correlated.
authors.affiliation: MRC Prion Unit/Neurogenetics, Imperial College School of Medicine at St Mary's, London W2 1PG, UK.
authors.forename: D
authors.initials: D
authors.lastname: Rossi
authors.forename: A
authors.initials: A
authors.lastname: Cozzio
authors.forename: E
authors.initials: E
authors.lastname: Flechsig
authors.forename: M A
authors.initials: MA
authors.lastname: Klein
authors.forename: T
authors.initials: T
authors.lastname: Rülicke
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*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D003360:Cosmids; D017931:DNA Primers; D058851:GPI-Linked Proteins; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D016366:Open Reading Frames; D010641:Phenotype; D011328:Prions / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D019076:Transgenes
chemical_list: D017931:DNA Primers; D058851:GPI-Linked Proteins; D011328:Prions; C122036:Prnd protein, mouse; D012333:RNA, Messenger