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

Publication

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

Journal Paper/Review - Jun 16, 2003

Flechsig Eckhard, Aguzzi Adriano, Götz Jürgen, Rülicke Thomas, Schwarz Petra, Cozzio Antonio, Rossi Daniela, Zuniga Armando, Leimeroth Rainer, Hegyi Ivan, Weissmann Charles

Citation

Flechsig E, Aguzzi A, Götz J, Rülicke T, Schwarz P, Cozzio A, Rossi D, Zuniga A, Leimeroth R, Hegyi I, Weissmann C. Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia. EMBO J 2003; 22:3095-101.

Type

Journal Paper/Review (English)

Journal

EMBO J 2003; 22

Publication Date

Jun 16, 2003

Issn Print

0261-4189

Pages

3095-101

Brief description/objective

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.