NR AXJA
AU Baumann,F.; Pahnke,J.; Radovanovic,I.; Bremer,J.; Rülicke,T.; Tolnay,M.; Aguzzi,A.
TI The Central Domain Represents an Essential Part for the Physiological Function of the Prion Protein
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.31
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Physiological function of PrPc still remains enigmatic. Recently we were able to demonstrate that expression of PrPdCD, an interstitial deletion mutant of PrP lacking 40 central residues (94-134), induces a rapidly progressive, lethal phenotype with extensive central and peripheral myelin degeneration (Baumann et al. EMBO 2007). This phenotype could be dose-dependently rescued by coexpression of full length PrP. We concluded that full length PrP is an essential component of the nervous system involved in the maintenance of myelin integrity. The ectopic expression of Doppel (Dpl) a structural homologue of PrP in the brain also leads to neuronal loss and myelin degeneration which can be rescued by coexpression of PrPc. Normal Dpl lacks functional domains similar to central domain and octarepeat region of PrPc. We now report that expression of chimeric fusion proteins of PrPc and Dpl do not show toxicity and can even partially substitute PrPc function. These results indicate an essential role of the hydrophobic core domain of PrP for the normal physiological function of PrPc.
AD F. Baumann, J. Bremer, A. Aguzzi, Institute for Neuropathology, University Hospital Zürich, Switzerland; J. Pahnke, Neurological Clinic, University of Rostock, Germany; I. Radovanovic, Department of Neurosurgery, University Hospital of Geneva, Switzerland; T. Rulicke, Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Austria; M. Tolnay, Neuropathology, University Hospital Basel, Switzerland
SP englisch
PO Schottland