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Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia
Author(s) -
Flechsig Eckhard,
Hegyi Ivan,
Leimeroth Rainer,
Zuniga Armando,
Rossi Daniela,
Cozzio Antonio,
Schwarz Petra,
Rülicke Thomas,
Götz Jürgen,
Aguzzi Adriano,
Weissmann Charles
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg285
Subject(s) - purkinje cell , biology , ataxia , knockout mouse , spinocerebellar ataxia , phenotype , cerebellum , exon , ectopic expression , microbiology and biotechnology , cell , programmed cell death , cell culture , apoptosis , genetics , neuroscience , gene
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.