NR AOTR
AU Hart,P.; Baybutt,H.N.; Tuzi,N.L.; Barron,R.M.; O'Neill,G.; Bruce,M.; Hunter,N.; Manson,J.
TI The TSE species barrier in gene targeted mice carrying the bovine PrP gene
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-24
PT Konferenz-Poster
AB
When attempting to transmit TSE disease between different species, incubation times are usually prolonged often beyond the life-span of the animal and not all animals appear susceptible to disease. This phenomenon know as the 'species barrier' has been proposed to be due to the differences in PrP protein sequence between the host and donor of infectivity. In vitro experiments have shown that the efficiency of conversion of PrPc to PrPsc is greatest when both proteins share identical amino acid sequence. In order to address the role of PrP sequence in the species barrier and to produce an appropriate murine model to study BSE, we have produced mice by replacement of the endogenous murine PrP coding region with the PrP bovine PrP gene. In this way PrP genes can be studied in the correct genomic location under the control of the murine regulatory sequences. This allows for normal expression patterns of the PrP gene in both CNS and peripheral tissues. We have used this approach to produce two inbred lines of mice expressing bovine PrP with either 5 (B5R) or 6 (B6R) octapeptide repeats and have crossed these lines to produce a heterozygous line expressing the two alleles. We have examined the level of PrP and its cellular location in the bovine PrP transgenic mice and have established it to be the same as the murine PrP protein in wild type mice.
The homozygous and heterozygous lines have been inoculated with BSE and vCJD to compare the incubation time of these agents in the transgenic and wild type mice. Titrations of the inoculum BSE have also been carried out to compare the susceptibility of the bovine transgenic and wild type (RIII and 129Ola) mice to the BSE inoculum. This will be compared to the titres obtained with bovine-bovine transmissions previously carried out (VLA) using the same inoculum. The results to date will be presented.
AD Patricia Hart, Herbert Baybutt, Nadia Tuzi, Rona Barron, Gerry O'Neill, Moira Bruce, Nora Hunter, Jean Manson, IAH, Neuropathogenesis Unit, Edinburgh, UK
SP englisch
PO Deutschland