Detection of cattle-derived BSE prions using transgenic mice overexpressing bovine PrPc
In interspecies transmissions of transmissible spongiform encephalopathies, the agent has to overcome a species barrier that is largely influenced by the rate of homology between the prion proteins (PrPc) of the two involved species. Generating transgenic mice expressing PrPc of a foreign species is an approach to develop TSE models that are at least partly devoid of a species barrier. The availability of such animals would enable the detection of low doses of infectivity in tissues or bodily fluids derived from other species. We generated transgenic mice that overexpress bovine PrPc (Tgbov XV mice) for the development of an improved detection assay for cattle derived BSE prions. These mice succumbed to the disease 250 days after inoculation with a brain homogenate from BSE diseased cattle. Diagnosis of BSE in transgenic mice was confirmed using Western blot, as well as histological and immunohistochemical methods. In contrast, transgenic mice overexpressing murine PrPc (tga2O mice) did not display shorter incubation times than nontransgenic RIII mice infected with the same inoculum. The expression of a chimaeric PrP of murine and bovine sequences rendered such mice partly, if not entirely resistant to an infection with the BSE agent.
Unable to display preview. Download preview PDF.
- 1.Buschmann A, Groschup MH (1998) Übertragbarkeit der spongiformen Enze-phalopathien unter natürlichen und experimentellen Bedingungen. In: Braun U (ed) BSp und andere spongiforme Enzephalopathien. Parey Verlag, Berlin, pp 51–76Google Scholar
- 2.Bradley R (1996) Experimental transmission of bovine spongiform encephalopathy. In: Court L, Dodet B (eds) Transmissible subacute spongiform enceph-alopathies: Prion Diseases. Elsevier, Paris, pp 51–56Google Scholar
- 6.Fischer M, Rulicke T, Raeber A, Sailer A, Moser M, Oesch B, Brandner S, Aguzzi A, Weissmann C (1996) Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO 15: 1255–1264Google Scholar
- 7.Fraser H, Foster JD (1993) Transmission to mice, sheep and goats and bioassay of bovine tissues. In: Bradley R, Marchant B (eds) Transmissible spongiform encephalopathies. Brussels, European Commission Agriculture, pp 145–160Google Scholar
- 13.Scott MR, Safar J, Telling G, Nguyen O, Groth D, Torchia M, Koehler R, Tremblay P, Walther D, Cohen FE, DeArmond SJ, Prusiner SB (1997) Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice. Proc Natl Acad Sci USA 94: 14279–14284PubMedCrossRefGoogle Scholar