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

被引:55
作者
Flechsig, E
Hegyi, I
Leimeroth, R
Zuniga, A
Rossi, D
Cozzio, A
Schwarz, P
Rülicke, T
Götz, J
Aguzzi, A
Weissmann, C [1 ]
机构
[1] Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland
[2] Univ Zurich, Inst Lab Tierkunde, Biol Zentrallab, CH-8091 Zurich, Switzerland
[3] Inst Neurol, Dept Neurodegenerat Dis, MRC, Prion Unit, London WC1N 3BG, England
关键词
cerebellar syndrome; Doppel protein; L7; promoter; prion protein; Purkinje cell loss;
D O I
10.1093/emboj/cdg285
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
PrP knockout mice with disruption of only the PrP-encoding region (Zurich 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 Zurich 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.
引用
收藏
页码:3095 / 3101
页数:7
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