NR ATQT
AU Brabeck,C.; Stitz,L.; Kloz,U.; van der Hoeven,F.; Bürkle,A.
TI Challenge of transgenic mice expressing a dominant-negative PrP deletion mutant with prions
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Structure of PrP and molecular determinants of infectivity STRCT-09
PT Konferenz-Poster
AB The prion protein (PrPc) is a GPI-anchored 35 kDa membrane glycoprotein essential for the pathogenesis of several inherited and transmissible neurodegenerative diseases such as scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. We have focused our interest on the so-called TM1 region of PrPc (codons 110-135) being one of the most highly conserved regions of the molecule. It has been proposed that the TM1 domain plays an important role in the conversion process of PrPc into PrPsc. In previous work, we have constructed a deletion mutant lacking codons 114-121 of PrPc termed delta114-121. Using persistently infected mouse neuroblastoma cells (Sc-N2a) as a model system for prion replication, we could show that delta114-121 itself cannot be converted into a protease-resistant isoform and that it furthermore behaves as a dominant-negative version of PrPc as the accumulation of endogenous PrPsc was significantly reduced in Sc-N2a cells in the presence of delta114-121 (Hölscher et al, J Virol 1998, 72:1153-9). To further investigate the dominant-negative effect of delta114-121 on prion replication in an in-vivo system, we have created transgenic mice expressing the deletion mutant either on a Prnp+/+ or Prnp-/- background. Analysis of delta114-121 mice revealed that the animals are viable and fertile and do not show any gross phenotypic changes. First results of inoculation experiments with transgenic delta114-121 animals will be discussed.
AD Christine Brabeck, Alexander Bürkle, Molecular Toxicology Group, University of Konstanz, Konstanz, Germany; Lothar Stitz, Institute of Immunology, Friedrich-Loeffler-Institute, Tübingen, Germany; Ulrich Kloz, Frank van der Hoeven, Transgenic Core Facility, Deutsches Krebsforschungszentrum, Heidelberg, Germany
SP englisch
PO Deutschland