NR AXOA
AU Hart,P.; Plinston,C.; Baybutt,H.; Blackford,L.; Appleby,K.; Gall,E.; Manson,J.C.; Barron,R.M.
TI Susceptibility of Gene Targeted Bovine Transgenic Mice to BSE Derived TSE Isolates
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.12
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
A characteristic of the Bovine Spongiform Encephalopathy (BSE) strain is its stability on transmission through different species when strain typed in a wild type (WT) mouse panel. However it is unknown whether the BSE strain maintains its pathogenicity in cattle following passage through different species, or if the host range is altered following subpassage within a species. In order to assess the pathogenicity in cattle of different BSE derived TSE strains, gene targeted transgenic (Tg) mice homozygous for bovine PrP with either 5 (B5) or 6 (B6) octapeptide repeats were inoculated intracerebrally with BSE which had been passaged through sheep (experimental sheep BSE), humans (vCJD) or wild type lines of mice (301V and 301C mouse passaged strains). Bovine Tg mice showed a high level of susceptibility to cattle BSE, experimental sheep BSE and vCJD, accompanied by similar incubation times, patterns of vacuolation and PrP deposition. 301V and 301C mouse passaged BSE strains however did not transmit efficiently to bovine Tg mice. While 301C showed equally poor transmission to both B5 and B6 lines, 301V transmitted to B6 mice with slightly higher susceptibility but similar long incubation times to B5 Tg mice. In all cases, incubation times observed in WT mice were shorter than in bovine Tg mice.
Previous studies have shown that transgenic mice overexpressing bovine PrP are highly susceptible to BSE with short incubation times. However when gene targeted bovine Tg mice (with wild type expression of PrP) are infected with BSE they still show 100% susceptibility, but with incubation times that are extended compared to WT mice. Transmissions from humans and sheep infected with BSE gave similar results indicating that sequence compatibility is not essential for efficient BSE infection. Unlike previous studies using overexpressing Tg mice, we saw no evidence of increased virulence of BSE after passage through sheep. Similar disease profiles were produced in Bovine Tg mice from both sheep BSE and vCJD, suggesting little alteration to strain characteristics following transmission through these species. However transmission and stabilisation of BSE in mice appears to have altered the strain properties, making it less transmissible to cattle.
AD P. Hart, C. Plinston, H. Baybutt, L. Blackford, K. Appleby, E. Gall, J. Manson, R. Barron, Roslin Institute, Neuropathogenesis Unit, UK
SP englisch
PO Schottland