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:

Altered circadian activity rhythms and sleep in mice devoid of prion protein

Nature volume 380, pages 639–642 (1996)Cite this article

Abstract

THERE is a wealth of data supporting a central role for the prion protein (PrP) in the neurodegenerative prion diseases of both humans and other species1, yet the normal function of PrP, which is expressed at the cell surface of neurons and glial cells2,3, is unknown. It has been speculated that neuropathology may be due to loss of normal function of PrP (ref. 4). Here we show that in mice devoid of PrP there is an alteration in both circadian activity rhythms and sleep patterns. To our knowledge, this is the first null mutation that has been shown to affect sleep regulation and our results indicate that the pathology of at least one of the inherited prion diseases, fatal familial insomnia5, where there is a profound alteration in sleep and the daily rhythms of many hormones6–10, may be related to the normal function of the prion protein.

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
Buy now

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

Similar content being viewed by others

References

  1. Prusiner, S. B. Science 252, 1515–1522 (1991).

    Article  ADS  CAS  Google Scholar 

  2. Manson, J., McBride, P. & Hope, J. Neurodegeneration 1, 45–52 (1992).

    Google Scholar 

  3. Moser, M., Colello, R. J., Pott, U. & Oesch, B. Neuron 14, 509–517 (1995).

    Article  CAS  Google Scholar 

  4. Collinge, J. et al. Nature 370, 295–297 (1994).

    Article  ADS  CAS  Google Scholar 

  5. Lugaresi, E. et al. New Engl. J. Med. 315, 997–1003 (1986).

    Article  CAS  Google Scholar 

  6. Medori, R. et al. New Engl. J. Med. 326, 444–449 (1992).

    Article  CAS  Google Scholar 

  7. Montagna, P., Cortelli, P., Gambetti, P. & Lugaresi, E. Adv. Neuroimmun. 5, 13–21 (1995).

    Article  CAS  Google Scholar 

  8. Portaluppi, F. et al. J. clin. Endocr. Metab. 78, 1075–1078 (1994).

    CAS  PubMed  Google Scholar 

  9. Gambetti, P., Parchi, P., Peterson, R. B., Chen, S. G. & Lugaresi, E. Brain Path. 5, 43–51 (1995).

    Article  CAS  Google Scholar 

  10. Reder, A. T. et al. Neurology 45, 1068–1075 (1995).

    Article  CAS  Google Scholar 

  11. Manson, J. C. et al. Molec. Neurobiol. 8, 121–127 (1994).

    Article  CAS  Google Scholar 

  12. Büeler, H. et al. Nature 356, 577–581 (1992).

    Article  ADS  Google Scholar 

  13. Manson, J. C. et al. Neurodegeneration 4, 113–115 (1995).

    Article  CAS  Google Scholar 

  14. Possidente, B. & Stephan, F. K. Behavl Genet. 18, 109–117 (1988).

    Article  CAS  Google Scholar 

  15. Schwartz, W. J. & Zimmerman, P. J. Neurosci. 10, 3685–3694 (1990).

    Article  CAS  Google Scholar 

  16. Fischer, M. et al. EMBO J. (in the press).

  17. Yamada, N., Shimoda, K., Ohi, K., Takahashi, S. & Takahashi, K. Physiol. Behav. 42, 87–91 (1988).

    Article  CAS  Google Scholar 

  18. Hotz Vitaterna, M. et al. Science 264, 719–725 (1994).

    Article  ADS  Google Scholar 

  19. Bult, A., Hiestand, L., Van der Zee, E. A. & Lynch, C. Brain Res. Bull. 32, 623–627 (1993).

    Article  CAS  Google Scholar 

  20. Valatx, J. L., Bugat, R. & Jouvet, M. Nature 238, 226–227 (1972).

    Article  ADS  CAS  Google Scholar 

  21. Valatx, J. L. & Bugat, R. Brain Res. 69, 315–330 (1974).

    Article  CAS  Google Scholar 

  22. Friedman, J. K. Physiol. Behav. 12, 169–175 (1974).

    Article  Google Scholar 

  23. Borbély, A. A. In: Kryger M. H., Roth T., Dement W. C. (eds) Principles and Practice of Sleep Medicine 2nd edn, 309–320 (Saunders, Philadelphia, 1994).

  24. Tobler, I. & Borbély, A. A. Electroenceph. Clin. Neurophysiol. 64, 74–76 (1986).

    Article  CAS  Google Scholar 

  25. Westaway, D. & Prusiner, S. P. Nucleic Acids Res. 14, 2035–2044 (1986).

    Article  CAS  Google Scholar 

  26. Deboer, T., Franken, P. & Tobler, I. J. Comp. Physiol. A. 174, 145–155 (1994).

    Article  CAS  Google Scholar 

  27. Franken, P., Dijk, D. J., Tobler, I. & Borbély, A. A. Am. J. Physiol. 261, R198–208 (1991).

    CAS  PubMed  Google Scholar 

  28. Deboer, T. & Tobler, I. Brain Res. 670, 153–156 (1995).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. M. Fischer: Institute of Molecular Biology, Department I, University of Zürich, 8093 Zürich, Switzerland

  2. T. Rülicke: Central Biological Laboratory, University Hospital, 8091 Zürich, Switzerland

  3. M. Moser and B. Oesch: Brain Research Institute, University of Zürich, 8029 Zürich, Switzerland

  4. P. A. McBride and J. C. Manson: Institute for Animal Health, BBSRC and MRC Neuropathogenesis Unit, Edinburgh EH9 3JF, UK

Authors and Affiliations

  1. Institute of Pharmacology, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland

    I. Tobler, S. E. Gaus, T. Deboer, P. Achermann, M. Fischer, T. Rülicke, M. Moser, B. Oesch, P. A. McBride & J. C. Manson

Authors
  1. I. Tobler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. E. Gaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Deboer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Achermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. Rülicke
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B. Oesch
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P. A. McBride
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J. C. Manson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tobler, I., Gaus, S., Deboer, T. et al. Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature 380, 639–642 (1996). https://doi.org/10.1038/380639a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/380639a0

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

Advanced 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