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.

  • Brief Communication
  • Published:

A candidate gene for human neurodegenerative disorders: a rat PKCγ mutation causes a Parkinsonian syndrome

Abstract

Rats harboring the agu mutation have altered behavior1 and brain pathology1 resembling human Parkinsonian syndromes2; notably, they have a movement disorder and age-progressive dysfunction and death of neurons in the midbrain (substantia nigra pars compacta) that use dopamine as a neurotransmitter. We present evidence that this phenotype is due to a mutation in the rat protein kinase Cγ (in rat, Prkcg; in mouse, Prkcc; in human, PRKCG) gene, which generates a premature stop codon, drastically reducing the level of synthesis of the catalytic domain of the brain-specific protein kinase Cγ protein.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Comparison of agu mutant (AS/AGU) and wild-type (AS) PKCγ cDNA sequences.
Figure 2: Absence of PKCγ immunoreactivity in agu mutant brain protein extracts and brain tissue.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Payne, A. P. et al. J. Anat. 196, 629–633 (2000).

    Article  CAS  Google Scholar 

  2. Lang, A. E. & Lozano, A. M. N. Engl. J. Med. 339, 1044–1053 (1998).

    Article  CAS  Google Scholar 

  3. Serikawa, T. et al. Genetics 131, 701–721 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Hashimoto, T. et al. J. Neurosci. 8, 1678–1683 (1988).

    Article  CAS  Google Scholar 

  5. Saito, N., Kikkawa, U., Nishizuka, Y. & Tanaka, C. J. Neurosci. 8, 369–382 (1988).

    Article  CAS  Google Scholar 

  6. Hug, H. & Sarre, T. F. Biochem. J. 291, 329–343 (1993).

    Article  CAS  Google Scholar 

  7. Sutton, R. B., Davletov, B. A., Berghuis, A. M., Südhof, T. C. & Sprang, S. R. Cell 80, 929–938 (1995).

    Article  CAS  Google Scholar 

  8. Tanaka, C. & Nishizuka, Y. Annu. Rev. Neurosci. 17, 551–567 (1994).

    Article  CAS  Google Scholar 

  9. Zirpel, L., Lippe, W. R. & Rubel, E. W. J. Neurophysiol. 79, 2288–2302 (1998).

    Article  CAS  Google Scholar 

  10. Polymeropoulos, M. H. Ann. NY Acad. Sci. 920, 28–32 (2000).

    Article  CAS  Google Scholar 

  11. Jaken, S. & Parker, P. J. Bioessays 22, 245–254 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Medical Research Council, the Parkinson's Disease Society, the Robertson Trust and Neuropa. N.J.C, M.B.D.A. and M.C. were recipients of BBSRC studentships, and A.S.M was a recipient of an MRC HGMP studentship. The work was approved by the University of Glasgow Ethical Review Committee and by the UK Home Office.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Wayne Davies.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Craig, N., Durán Alonso, M., Hawker, K. et al. A candidate gene for human neurodegenerative disorders: a rat PKCγ mutation causes a Parkinsonian syndrome. Nat Neurosci 4, 1061–1062 (2001). https://doi.org/10.1038/nn740

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn740

This article is cited by

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