NR AKEH
AU Rossi,D.; Cozzio,A.; Flechsig,E.; Klein,M.A.; Rülicke,T.; Aguzzi,A.; Weissmann,C.
TI Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain
QU EMBO Journal 2001 Feb 15; 20(4): 694-702
PT journal article
AB 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.
MH Alleles; Animal; Ataxia/genetics/*pathology; Base Sequence; Brain/*metabolism; Cosmids; DNA Primers; Immunoblotting; Immunohistochemistry; Mice; Mice, Knockout; Multigene Family; Open Reading Frames; Phenotype; Prions/genetics/*metabolism/*physiology; Purkinje Cells/*physiology; RNA, Messenger/genetics; Support, Non-U.S. Gov't; Transgenes
AD MRC Prion Unit/Neurogenetics, Imperial College School of Medicine at St Mary's, London W2 1PG, UK
SP englisch
PO England