NR AXNQ
AU Griffiths,P.C.; Plater,J.M.; Chave,A.; Tout,A.C.; Cawthraw,S.; Jayasena,D.; Scholey,S.; Dexter,I.; Lockey,R.; Spiropoulos,J.; Windl,O.
TI Transmission of Ruminant TSEs to Transgenic Mice Expressing Bovine, Kudu and Sheep PrPs
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Epidemiology, Risk Assessment and Transmission P04.115
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Transgenic PrP mouse models offer the prospect of bioassays of greater susceptibility and sensitivity for TSE agents compared to conventional mouse lines. Overexpressing transgenic models are potentially more sensitive than the natural host in detecting prion infectivity, and also represent more economically viable approaches than bioassay in cattle and sheep.
Aim: The aim of this Defra-funded study was to produce bioassay models of improved efficiency for the evaluation of BSE and scrapie by generating transgenic PrP mice overexpressing bovine, kudu and sheep PrPs, and to assess the susceptibility of characterised lines by challenge with TSEs.
Methods: Transgenes containing full-length bovine PrP and chimeric forms of kudu and sheep PrPs were prepared and used to generate and breed mice on a FVB/PrP knockout background. Transgene expression levels in brain and other tissues and copy number were determined. Mice challenged with TSE agents were monitored for the development of clinical signs and prion disease was confirmed by Western blot detection of PrPsc and neuropathology.
Results: Transgenic lines expressing a range of PrPs in brain and other tissues were produced and bred to homozygosity on a PrP null background. Homozygous and heterozygous mice were challenged with a range of TSE agents (BSE, classical and atypical scrapie). Homozygous bovinised mice showed susceptibility to BSE and scrapie, with reduced incubation periods in comparison to wild-type controls and heterozygous mice.
Discussion: Transmission studies of TSE agents in the transgenic lines produced are in progress. Preliminary findings indicated susceptibility and reduced incubation periods in several transgenic lines, but further results are awaited. Western blotting and neuropathological analyses of challenged mice will be conducted and should reveal the characteristics associated with different TSE agents and particular transgenic PrPs.
AD P.C. Griffiths, J.M. Plater, A. Chave, Anna C. Tout, S. Cawthraw, D. Jayasena, O. Windl, Veterinary Laboratories Agency, Molecular Pathogenesis and Genetics Department, UK; S. Scholey, I. Dexter, Veterinary Laboratories Agency, Animal Services Unit, UK; R. Lockey, J. Spiropoulos, Veterinary Laboratories Agency, Neuropathology Section, Pathology Department, UK
SP englisch
PO Schottland