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.

Disruption of the nuclear hormone receptor RORα in staggerer mice

Nature volume 379, pages 736–739 (1996)Cite this article

A Correction to this article was published on 23 May 1996

Abstract

HOMOZYGOUS staggerer (sg) mice show a characteristic severe cerebellar ataxia due to a cell-autonomous defect in the development of Purkinje cells1,2. These cells show immature morphology, synaptic arrangement, biochemical properties and gene expression, and are reduced in numbers3–12. In addition, sg heterozygotes show accelerated dendritic atrophy and cell loss13, suggesting that sg has a role in mature Purkinje cells. Effects of this mutation on cerebellar development have been studied for 25 years, but its molecular basis has remained unknown. We have genetically mapped staggerer to an interval of 160 kilobases on mouse chromosome 9 which was found to contain the gene encoding RORα, a member of the nuclear hormone-receptor superfamily. Staggerer mice were found to carry a deletion within the RORα gene that prevents translation of the ligand-binding homology domain. We propose a model based on these results, in which RORα interacts with the thyroid hormone signalling pathway to induce Purkinje-cell maturation.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

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

References

  1. Sidman, R. L., Lane, P. W. & Dickie, M. M. Science 137, 610–612 (1962).

    Article  ADS  CAS  Google Scholar 

  2. Herrup, K. & Mullen, R. J. Brain Res. 178, 443–457 (1979).

    Article  CAS  Google Scholar 

  3. Sotelo, C. & Changeux, J.-P. Brain Res. 67, 519–526 (1974).

    Article  CAS  Google Scholar 

  4. Sotelo, C. Adv. Neurol. 12, 335–351 (1975).

    CAS  PubMed  Google Scholar 

  5. Crepel, F., Delhaye-Bouchaud, N., Guastavino, J. M. & Sampaio, I. Nature 283, 483–484 (1980).

    Article  ADS  CAS  Google Scholar 

  6. Landis, D. M. & Sidman, R. L. J. comp. Neurol. 179, 831–863 (1978).

    Article  CAS  Google Scholar 

  7. Mariani, J. & Changeux, J.-P. J. Neurobiol. 11, 41–50 (1980).

    Article  CAS  Google Scholar 

  8. Hatten, M. E. & Messer, A. Nature 276, 504–506 (1978).

    Article  ADS  CAS  Google Scholar 

  9. Trenkner, E. Nature 277, 566–567 (1979).

    Article  ADS  CAS  Google Scholar 

  10. Edelman, G. M. & Chuong, C. M. Proc. natn. Acad. Sci. U.S.A. 79, 7036–7040 (1982).

    Article  ADS  CAS  Google Scholar 

  11. Herrup. K. & Müllen, R. J. Brain Res. 227, 475–485 (1981).

    Article  CAS  Google Scholar 

  12. Herrup. K. Brain Res. 313, 267–274 (1983).

    Article  CAS  Google Scholar 

  13. Zanjani, H. S., Mariani, J., Delhaye-Bouchaud, N. & Herrup, K. Brain Res. Dev. 67, 153–160 (1992).

    Article  CAS  Google Scholar 

  14. Dietrich, W. F. et al. Nature Genet. 7, 220–245 (1994).

    Article  CAS  Google Scholar 

  15. Kusumi, K., Smith, J. S., Segre J. A., Koos, D. S. & Lander, E. S. Mamm. Genome 4, 391–392 (1993).

    Article  CAS  Google Scholar 

  16. Becker-André, M., André, E. & DeLamarter, J. F. Biochem. Biophys. Res. Commun. 194, 1371–1379 (1993).

    Article  Google Scholar 

  17. Giguere, V. et al. Genes Dev. 8, 538–553 (1994).

    Article  CAS  Google Scholar 

  18. Giguere, V., McBroom, L. D. & Flock, G. Molec. cell. Biol. 15, 2517–2526 (1995).

    Article  CAS  Google Scholar 

  19. McBroom, L. D., Flock, G. & Giguere, V. Molec. cell. Biol. 15, 796–808 (1995).

    Article  CAS  Google Scholar 

  20. Herrup, K. & Mullen. R. J. Brain Res. 172, 1–12 (1979).

    Article  CAS  Google Scholar 

  21. Hatten, M. E. & Heintz, N. A. Rev. Neurosci. 18, 385–408 (1995).

    Article  CAS  Google Scholar 

  22. Trenkner, E. & Hoffmann, M. K. J. Neurosci. 6, 1733–1737 (1986).

    Article  CAS  Google Scholar 

  23. Legrand, J. Trends Neurosci. 2, 234–236 (1979).

    Article  Google Scholar 

  24. Messer, A. J. Neurochem. 51, 888–891 (1988).

    Article  CAS  Google Scholar 

  25. Zou, L., Hagen, S. G., Strait, K. A. & Oppenheimer, J. H. J. biol. Chem. 269, 13346–13352 (1994).

    CAS  PubMed  Google Scholar 

  26. Tini, M., Tsui, L. C. & Giguere, V. Molec. Endocr. 8, 1494–1506 (1994).

    CAS  PubMed  Google Scholar 

  27. Forman, B. M. et al. Molec. Endocr. 8, 1253–1261 (1994).

    CAS  PubMed  Google Scholar 

  28. Tini, M., Fraser, R. A. & Giguere, V. J. biol. Cnem. 270, 20156–20161 (1995).

    Article  CAS  Google Scholar 

  29. Forman, B. M., Umesono, K., Chen, J. & Evans, R. M. Cell 81, 541–550 (1995).

    Article  CAS  Google Scholar 

  30. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning; A Laboratory Manual (Cold SpringHarbor Laboratory Press, Cold Spring Harbor, New York, 1989).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, Nine Cambridge Centre, Cambridge, Massachusetts, 02142, USA

    Bruce A. Hamilton, Anne W. Kerrebrock, Trevor L. Hawkins, William FitzHugh, Kenro Kusumi, Ken L. Mueller, Victor van Berkel, Bruce W. Birren, Leonid Kruglyak & Eric S. Lander

  2. The Jackson Laboratory, Bar Harbor, Maine, 04609, USA

    Wayne N. Frankel

  3. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Kenro Kusumi & Eric S. Lander

  4. Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, 37831-8077, USA

    Liane B. Russell

Authors
  1. Bruce A. Hamilton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wayne N. Frankel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne W. Kerrebrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Trevor L. Hawkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William FitzHugh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kenro Kusumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liane B. Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ken L. Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Victor van Berkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Bruce W. Birren
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Leonid Kruglyak
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Eric S. Lander
    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

Hamilton, B., Frankel, W., Kerrebrock, A. et al. Disruption of the nuclear hormone receptor RORα in staggerer mice. Nature 379, 736–739 (1996). https://doi.org/10.1038/379736a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/379736a0

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