Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia

Flechsig, Eckhard, Hegyi, Ivan, Leimeroth, Rainer, Zuniga, Armando, Rossi, Daniela, Cozzio, Antonio, Schwarz, Petra, Rulicke, Thomas, Gotz, Juergen, Aguzzi, Adriano and Weissmann, Charles (2003) Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia. EMBO Journal, 22 12: 3095-3101. doi:10.1093/emboj/cdg285


Author Flechsig, Eckhard
Hegyi, Ivan
Leimeroth, Rainer
Zuniga, Armando
Rossi, Daniela
Cozzio, Antonio
Schwarz, Petra
Rulicke, Thomas
Gotz, Juergen
Aguzzi, Adriano
Weissmann, Charles
Title Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia
Journal name EMBO Journal   Check publisher's open access policy
ISSN 0261-4189
1460-2075
Publication date 2003-06-16
Sub-type Article (original research)
DOI 10.1093/emboj/cdg285
Open Access Status Not yet assessed
Volume 22
Issue 12
Start page 3095
End page 3101
Total pages 7
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract 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.
Keyword Cerebellar syndrome
Doppel protein
L7 promoter
Prion protein
Purkinje cell loss
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Ageing Dementia Research Publications
 
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