NR AXXE
AU Steinacker,P.; Schulze,B.; Schulze,E.; Hobert,O.; Brechlin,P.; Lehnert,S.; Cepek,L.; Otto,M.
TI Caenorhabditis Elegans as a Heterologous Expression System for Human Prion Protein
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.31
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Heterologous expression of prion protein is widely used for the analysis of its physiological and pathophysiological properties. Different cell culture systems and animal models like hamster or mice are used to examine PrP function and conditions that influence infection or infectiosity for several aims with the known advantages and disadvantages.
For further characterization of PrP function and interaction-proteins we established the nematode C. elegans, that has no endogenous PrP, as an expression system of human PrP. Although C. elegans is a simple eucaryotic organism, cellular mechanisms and biochemical pathways resemble in many points that of humans. Additionally the worms are easy to culture and to manipulate and have a short generation time.
The aim of this work was to generate a model for examination of PrP. We characterized PrP transformed C.elegans strains by determination of life spans and motoric phenotypes and also by applying proteomic approches (difference gel electrophoresis (2D-DIGE). As control-worms we generated a strain that was transformed with the empty pBY871 vector. Whereas the life spans and readouts of thrashing assay, radial locomotion assay and quantification of reversals and body bends don't differ between PrP- and control-worms we found proteins that are differentially expressed in PrPworms compared to controls. We identified proteins that were either up or down regulated dependent on PrP expression, e.g translation elongation factor and an aconitase.
Next steps will be to express mutant PrP associated with neurodegeneration and / or infectiosity and characterize again the proteome and genome compared to PrPc. If there is a phenotypical change the generated model could be useful not only for the analysis of general PrP trafficking and turnover but also for the study of infection cofactors.
AD P. Steinacker, S. Lehnert, L. Cepek, M. Otto, University Ulm, Neurology, Germany; B. Schulze, E. Schulze, Albert-Ludwigs-University, Germany; O. Hobert, Columbia University, USA; P. Brechlin, Georg-August-University, Germany
SP englisch
PO Schottland