Arrighi
Fakultäten » Medizinische Fakultät » Neuropathologie, Institut für » Prof. Dr. Adriano Aguzzi » Arrighi
Completed research project
| Title / Titel | Validation and characterization of novel interaction partners of PrPC and Doppel | ||||
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| Abstract (PDF, 14 KB) | |||||
| Summary / Zusammenfassung | There is distinct genetic evidence for an interaction between PrPC and Doppel. While Doppel is severely neurotoxic to Purkinje cells in the cerebellum, toxicity is abolished by co-expression of PrPC. This indicates that the two proteins interact genetically, if not physically. To study the details of these interactions, we have generated and characterized Doppel-deficient mice. Dpl deficiency did not interfere with embryonic and postnatal development, but resulted in male sterility. We have generated lentiviral vectors for gene transduction of Doppel to any given tissue including postmitotic cells. We are currently assessing whether injection of Doppel-transducing lentivirus into seminiferous tubuli of Doppel-deficient mice can restore fertility. If so, this will yield a fast, efficient model that is easy to manipulate and will allow to determine precisely structure-function relationship of the prion and Doppel proteins. |
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| Publications / Publikationen | Behrens A., Genoud N., Naumann H., Rülicke T., Janett F., Heppner FL., Ledermann B. and Aguzzi A. (2002). Absence of the prion protein homologue Doppel causes male sterility. EMBO. 21, 1-7.Ikawa M., Tergaonkar V., Ogura A., Ogonuki N., Inoue K., Verma IM. (2002). Restoration of spermatogenesis by lentiviral gene transfer : offspring from infertile mice. PNAS, 99, 7524-7529. | ||||
| Keywords / Suchbegriffe | Fertility, testis, lentivirus, Doppel. | ||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
Others EMBO |
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| Duration of Project / Projektdauer | Jan 2002 to Dec 2005 |