NR AOQA
AU Barron,R.M.; Baybutt,H.N.; McCormack,J.; Thomson,V.; King,D.; Melton,D.W.; Manson,J.C.
TI Control of Scrapie Incubation Time by L108F and T189V Polymorphisms in Murine PrP
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - IV-04
PT Konferenz-Poster
AB Polymorphisms in the murine Prnp gene at amino acids 108 and 189 are thought to be responsible for the control of scrapie incubation time in mice. Mice encoding 108L/189T contain the Prnpa gene, while mice encoding 108F/189V contain the Prnpb gene. We have previously shown that the introduction of 108F/189V into the murine Prnpa gene by gene targeting (FV/FV) reduces the incubation time of 301V to a level similar to that observed in VM (Prnpb) mice. Transmission of five further strains of mouse passaged scrapie by both intracerebral and intraperitoneal routes of inoculation have confirmed these results and prove that amino acids 108 and 189 exert the major control on incubation time of scrapie in laboratory mice. However, incubation times in FV/FV mice are not identical to those observed in VM mice, suggesting that other genetic elements are also involved in control of incubation time, but to a lesser degree. In order to identify whether either one or both polymorphisms are required to produce this effect, we have produced two further gene targeted models which express each polymorphism separately (LV/LV and FT/FT). As the polymorphisms have been introduced by gene targeting we can directly compare wild type mice (LT/LT), FV/FV mice, LV/LV mice, FT/FT mice and their heterozygous crosses to examine the role of each polymorphism in the control of scrapie incubation time. Inoculations with two mouse scrapie strains have established that that all genotypes are susceptible to infectivity, and that both polymorphisms are involved in the control in scrapie incubation time in mice. Possible models for the mechanism of control involving these two amino acids will be discussed.
AD R.M. Barron, H.N. Baybutt, J. McCormack, V. Thomson, D. King, J.C. Manson, Institute for Animal Health, UK; D.W. Melton, CRC Molecular Medicine Centre, UK
SP englisch
PO Deutschland