NR AXOG
AU Heikenwälder,M.; Margalith,I.; Haybäck,J.; Bänziger,S.; Hutter,G.; Nairz,K.; Heppner,F.; Sigurdson,C.; Speck,R.; Aguzzi,A.
TI Replication of Human Prions in a "Humanized" Mouse Model System
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.104
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases affecting both humans and a large variety of animals. Ethical constraints prevent most functional analyses of neuroimmunological aspects of TSEs in humans. By combining transgenesis and xenotransplantation, we have created an accurate animal model that circumvents such constraints (1). The bone marrow of immune compromised gC-/-RAG2-/- mice is reconstituted with CD34+ hematopoietic stem cells derived from the umbilical cord blood of healthy human newborns. By this we establish a "humanized" immune system in the mouse, which can be tested for its capability to replicate human prions in vivo. gC-/-RAG2-/- mice reconstituted with human CD34+ cells, homozygote for methionine at codon 129 of the human Prion gene (129M/M), were peripherally inoculated with brain homogenate derived from a sCJD patient (129MM). In contrast to unreconstituted control mice, we detected PrPsc in the spleens of reconstituted gC-/-RAG2-/- mice already at 60, 90 and 120 days post inoculation. Hereby, we established an in vivo assay to test how different polymorphisms of the engrafted human prion protein, expressed on human immune cells, permit the replication of various, potentially human pathogenic, prion strains (e.g. chronic wasting disease; scrapie). In addition, this may yield an extremely sensitive, ethically acceptable and reasonably rapid test for human prion infectivity.
1. Traggiai et al., SCIENCE 2004.
AD M. Heikenwälder, I. Margalith, J. Haybäck, G. Hutter, K. Nairz, F. Heppner, C. Sigurdson, A. Aguzzi, University Hospital Zürich, Pathology, Switzerland; S. Bänziger, R. Speck, University Hospital Zürich, Infectiology, Switzerland
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterautoren: M. Heikenwalder, I. Margalith, J. Haybaeck, M. Polymenidou, M. Kurrer, N. Zeller, P. Schwarz und A. Aguzzi; Postertitel: Granulomatous inflammation induces prion accumulation and replication)