Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain

Publication

Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain

Journal Paper/Review - Feb 15, 2001

Rossi D, Cozzio Antonio, Flechsig E, Klein M A, Rülicke T, Aguzzi A, Weissmann C

Citation

Rossi D, Cozzio A, Flechsig E, Klein M, Rülicke T, Aguzzi A, Weissmann C. Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain. EMBO J 2001; 20:694-702.

Type

Journal Paper/Review (English)

Journal

EMBO J 2001; 20

Publication Date

Feb 15, 2001

Issn Print

0261-4189

Pages

694-702

Brief description/objective

PrP knockout mice in which only the open reading frame was disrupted ('Zürich I') remained healthy. However, more extensive deletions resulted in ataxia, Purkinje cell loss and ectopic expression in brain of Doppel (Dpl), encoded by the downstream gene, PRND: A new PrP knockout line, 'Zürich II', with a 2.9 kb PRNP: deletion, developed this phenotype at approximately 10 months (50% morbidity). A single PRNP: allele abolished the syndrome. Compound Zürich I/Zürich II heterozygotes had half the Dpl of Zürich II mice and developed symptoms 6 months later. Zürich II mice transgenic for a PRND:-containing cosmid expressed Dpl at twice the level and became ataxic approximately 5 months earlier. Thus, Dpl levels in brain and onset of the ataxic syndrome are inversely correlated.