Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain

This is a preview of subscription content, access via your institution

Access options

Buy this article

Purchase on Springer Link

Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Assessment of the efficacy of reconstitution of the lymphohaemopoietic system by adoptive transfer of LSCs or of T-cell-depleted bone marr.
Figure 2: Analysis of immune response to PrP in grafted animals.

References

  1. Büeler, H. R.et al. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 256, 577–582 (1992).

    Article  ADS  Google Scholar 

  2. Büeler, H. R.et al. Mice devoid of PrP are resistant to scrapie. Cell 73, 1339–1347 (1993).

    Google Scholar 

  3. Brandner, S.et al. Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379, 339–343 (1996).

    Article  ADS  CAS  Google Scholar 

  4. Fischer, M.et al. Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO J. 15, 1255–1264 (1996).

    Google Scholar 

  5. Taraboulos, A.et al. Regional mapping of prion proteins in brain. Proc. Natl Acad. Sci. USA 89, 7620–7624 (1992).

    Google Scholar 

  6. Brandner, S.et al. Normal host prion protein (PrPC) required for scrapie spread within the central nervous system. Proc. Natl Acad. Sci. USA 93, 13148–13151 (1996).

    Google Scholar 

  7. Sailer, A., Bueler, H., Fischer, M., Aguzzi, A. & Weissmann, C. No propagation of prions in mice devoid of PrP. Cell 77, 967–968 (1994).

    Google Scholar 

  8. Fraser, H. & Dickinson, A. G. Pathogenesis of scrapie in the mouse: the role of the spleen. Nature 226, 462–463 (1970).

    Article  ADS  CAS  Google Scholar 

  9. Kitamoto, T., Muramoto, T., Mohri, S., Doh ura, K. & Tateishi, J. Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfeldt–Jakob disease. J. Virol. 65, 6292–6295 (1991).

    Google Scholar 

  10. O'Rourke, K. I., Huff, T. P., Leathers, C. W., Robinson, M. M. & Gorham, J. R. SCID mouse spleen does not support scrapie agent replication. J. Gen. Virol. 75, 1511–1514 (1994).

    Google Scholar 

  11. Lasmezas, C. I.et al. Immune system-dependent and -independent replication of the scrapie agent. J. Virol. 70, 1292–1295 (1996).

    Google Scholar 

  12. Brown, K. L., Stewart, K., Bruce, M. E. & Fraser, H. in Transmissible Subacute Spongiform Encephalopathies: Prion Diseases(eds Court L. &Dodet, B.) 159–166 (Elsevier, Paris, (1996)).

    Google Scholar 

  13. Kimberlin, R. H. & Walker, C. A. The role of the spleen in the neuroinvasion of scrapie in mice. Virus Res. 12, 201–211 (1989).

    Google Scholar 

  14. Fraser, H. & Dickinson, A. G. Studies of the lymphoreticular system in the pathogenesis of scrapie: the role of spleen and thymus. J. Comp. Pathol. 88, 563–573 (1978).

    Google Scholar 

  15. Fraser, H.et al. Replication of scrapie in spleens of SCID mice follows reconstitution with wild-type mouse bone marrow. J. Gen. Virol. 77, 1935–1940 (1996).

    Google Scholar 

  16. Isenmann, S., Brandner, S., Kuhne, G., Boner, J. & Aguzzi, A. Comparative in vivo and pathological analysis of the blood–brain barrier in mouse telencephalic transplants. Neuropathol. Appl. Neurobiol. 22, 118–128 (1996).

    Google Scholar 

  17. Kimberlin, R. H., Hall, S. M. & Walker, C. A. Pathogenesis of mouse scrapie. Evidence for direct neural spread of infection to the CNS after injection of sciatic nerve. J. Neurol. Sci. 61, 315–325 (1983).

    Google Scholar 

  18. Beekes, M., Baldauf, E. & Diringer, H. Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie. J. Gen. Virol. 77, 1925–1934 (1996).

    Google Scholar 

  19. Büeler, H.et al. High prion and PrPSc levels but delayed onset of disease in scrapie-inoculated mice heterozygous for a disrupted PrP gene. Mol. Med. 1, 19–30 (1994).

    Google Scholar 

  20. Brown, P., Wolff, A. & Gajdusek, D. C. Asimple and effective method for inactivating virus infectivity in formalin-fixed tissue samples from patients with Creutzfeldt–Jakob disease. Neurology 40, 887–890 (1990).

    Google Scholar 

  21. Prusiner, S. B.et al. Measurement of the scrapie agent using an incubation time interval assay. Ann. Neurol. 11, 353–358 (1982).

    Google Scholar 

Download references

Acknowledgements

We thank R. Zinkernagel, U. Karrer, E. Flechsig and K. Riem for help with haemopoietic transfer. This study was supported by the Kanton of Zürich, by grants from the Schweizerischer Nationalfonds and Nationales Forschungsprogramm 38 (to A.A. and C.W.) by the European Union, Bundesamt für Veterinärwesen und für Gesundheit and Migros Foundation (A.A.), and by the Human Frontier Science Program (C.W.).

Author information

Authors and Affiliations

Authors

Additional information

Adriano Aguzzi: Correspondence and requests for materials should be addressed to A.A.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blättler, T., Brandner, S., Raeber, A. et al. PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain. Nature 389, 69–73 (1997). https://doi.org/10.1038/37981

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/37981

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing