Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1963
Flechsig, E; Hegyi, I; Leimeroth, R; Zuniga, A; Rossi, D; Cozzio, A; Schwarz, Petra; Rülicke, T; Götz, J; Aguzzi, A; Weissmann, Charles (2003). Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia. The EMBO Journal, 22(12):3095-3101.
PrP knockout mice with disruption of only the PrP-encoding region (Zürich I-type) remain healthy, whereas mice with deletions extending upstream of the PrP-encoding exon (Nagasaki-type) suffer Purkinje cell loss and ataxia, associated with ectopic expression of Doppel in brain, particularly in Purkinje cells. The phenotype is abrogated by co-expression of full-length PrP. Doppel is 25% similar to PrP, has the same globular fold, but lacks the flexible N-terminal tail. We now show that in Zürich I-type PrP-null mice, expression of N-terminally truncated PrP targeted to Purkinje cells also leads to Purkinje cell loss and ataxia, which are reversed by PrP. Doppel and truncated PrP probably cause Purkinje cell degeneration by the same mechanism.
|Item Type:||Journal Article, refereed|
|Communities & Collections:||04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine|
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Date:||16 June 2003|
|Deposited On:||11 Feb 2008 12:26|
|Last Modified:||27 Nov 2013 23:17|
|Publisher:||European Molecular Biology Organization ; Nature Publishing Group|
|Citations:||Web of Science®. Times Cited: 47|
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