NR AXIZ
AU Baumann,F.; Nairz,K.; Rülicke,T.; Aguzzi,A.
TI In-Vivo Identification of Functional Sub-Domains within Central Domain of the Cellular Prion Protein
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.24
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB The physiological function of PrPc still remains elusive. Mice devoid of PrP develop normally but are resistant to scrapie; introduction of a PrP transgene restores susceptibility to the disease. Recently we were able to demonstrate that expression of PrPdCD, a PrP variant 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 dosedependently rescued by coexpression of full length PrP. Here we extend our previous study by assessing the impact of the subdomains on the phenotype creating two novel transgenic mouse models - PrPdCC, a PrP variant lacking charged residues 94-110 and PrP, a PrP variant lacking hydrophobic core residues 111-134. Like PrP, PrP expression causes a progressive, lethal phenotype with similar severe alterations in central and peripheral white matter, while PrPdCC does not seem to provoke any obvious phenotype. PrPdCC does not show any alteration in the post translational processing while both PrPand PrPprevent the formation of the carboxyterminal fragment C1. We therefore propose that the absence of a neuroprotective activity associated with C1 formation may be responsible for the observed phenotypes.
AD F. Baumann, K. Nairz, A. Aguzzi, Institute for Neuropathology, University Hospital Zürich, Switzerland; T. Rulicke, Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Austria
SP englisch
PO Schottland