Abstract
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 ∼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 ∼5 months earlier. Thus, Dpl levels in brain and onset of the ataxic syndrome are inversely correlated.
| Original language | English |
|---|---|
| Pages (from-to) | 694-702 |
| Number of pages | 9 |
| Journal | EMBO Journal |
| Volume | 20 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Feb 15 2001 |
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Keywords
- Cerebellar syndrome
- Doppel protein
- Gene deletion
- Granule cells
- Prion protein
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain. / Rossi, Daniela; Cozzio, Antonio; Flechsig, Eckhard; Klein, Michael A.; Rülicke, Thomas; Aguzzi, Adriano; Weissmann, Charles.
In: EMBO Journal, Vol. 20, No. 4, 15.02.2001, p. 694-702.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain
AU - Rossi, Daniela
AU - Cozzio, Antonio
AU - Flechsig, Eckhard
AU - Klein, Michael A.
AU - Rülicke, Thomas
AU - Aguzzi, Adriano
AU - Weissmann, Charles
PY - 2001/2/15
Y1 - 2001/2/15
N2 - 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 ∼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 ∼5 months earlier. Thus, Dpl levels in brain and onset of the ataxic syndrome are inversely correlated.
AB - 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 ∼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 ∼5 months earlier. Thus, Dpl levels in brain and onset of the ataxic syndrome are inversely correlated.
KW - Cerebellar syndrome
KW - Doppel protein
KW - Gene deletion
KW - Granule cells
KW - Prion protein
UR - http://www.scopus.com/inward/record.url?scp=0035865398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035865398&partnerID=8YFLogxK
U2 - 10.1093/emboj/20.4.694
DO - 10.1093/emboj/20.4.694
M3 - Article
C2 - 11179214
AN - SCOPUS:0035865398
VL - 20
SP - 694
EP - 702
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 4
ER -