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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1946

Genoud, Nicolas; Behrens, A; Miele, G; Robay, D; Heppner, F L; Freigang, S; Aguzzi, A (2004). Disruption of Doppel prevents neurodegeneration in mice with extensive Prnp deletions. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 101(12):4198-4203.

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Abstract

The Prnp gene encodes the cellular prion protein PrP(C). Removal of its ORF does not result in pathological phenotypes, but deletions extending into the upstream intron result in cerebellar degeneration, possibly because of ectopic cis-activation of the Prnd locus that encodes the PrP(C) homologue Doppel (Dpl). To test this hypothesis, we removed Prnd from Prnp(o/o) mice by transallelic meiotic recombination. Balanced loxP-mediated ablation yielded mice lacking both PrP(C) and Dpl (Prn(o/o)), which developed normally and showed unimpaired immune functions but suffered from male infertility. However, removal of the Prnd locus abolished cerebellar degeneration, proving that this phenotype is caused by Dpl upregulation. The absence of compound pathological phenotypes in Prn(o/o) mice suggests the existence of alternative compensatory mechanisms. Alternatively, Dpl and PrP(C) may exert distinct functions despite having partly overlapping expression profiles.

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32 citations in Web of Science®
34 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:23 March 2004
Deposited On:11 Feb 2008 12:26
Last Modified:27 Nov 2013 18:05
Publisher:National Academy of Sciences
ISSN:0027-8424
Publisher DOI:10.1073/pnas.0400131101
PubMed ID:15007175

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