NR AOYM
AU Sabuncu,E.; Thanh-Lan Lai; Le Dur,A.; Laude,H.; Vilette,D.
TI PrP Variants with Opposite Disease Linkage: Cell Biology in Rov Cells
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-98
PT Konferenz-Poster
AB
Polymorphisms of PrP have been linked to the susceptibility to prion diseases in mice, sheep and humans and this linkage has been extensively illustrated during the last 5-10 years. Recently, long-term programs of breeding for genetic resistance to sheep scrapie have been launched in several European countries including UK and France. However, the mechanisms by which such polymorphisms operate are still poorly characterized and indeed, sheep of the genotype most resistant to scrapie have lately been reported to have succombed to BSE following intracerebral challenge (Houston et al., 2003).
Rov cells expressing a transfected ovine PrP gene are permissive to sheep prions (Vilette et al., 2001). We have generated Rov cells expressing a PrP allele associated either with high susceptibility (VRQ) or with resistance (ARR). We found that Rov cells expressing ARR-PrP are at least 1000-fold less efficient than VRQ-Rov cells to replicate prions (Sabuncu et al., 2003). This is the first direct evidence that natural PrP polymorphisms may affect prion susceptibility by controlling the efficiency of prion replication at the cell level.
We then investigated the biology of PrP variants in Rov cells using different techniques, such as association with detergent-resistant microdomains, cleavage with PIPL-C, detergent solubility assay and confocal imaging. Our results show differences in the biochemical properties of the two PrP variants with opposite disease linkage. These findings could be related with the difference in permissiveness of Rov cells to prion infection.
AD Elifsu Sabuncu, Thanh-Lan Lai, Annick Le Dur, Hubert Laude, Didier Vilette, INRA, France
SP englisch
PO Deutschland