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

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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.

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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.

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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.

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Author notes

  1. Nicola J. Craig and María B. Durán Alonso: The first two authors contributed equally to this work

Authors and Affiliations

  1. University of Glasgow, Institute of Biomedical and Life Sciences, Glasgow, G12 8QQ, Scotland, UK

    Nicola J. Craig, María B. Durán Alonso, Paul Shiels, Jacqueline M. Campbell, Neil K. Bennett, Maurice Canham, Denise Donald, Mary Gardiner, Desmond P. Gilmore, Andrew S. McCallion, David Russell, Anthony P. Payne, Roger G. Sutcliffe & R. Wayne Davies

  2. Neuropa, 54 Dumbarton Road, Glasgow, G11 6NU, Scotland, UK

    Nicola J. Craig, Kim L. Hawker, Thora A. Glencorse, Jacqueline M. Campbell, Kirsty Maitland, Andrew S. McCallion & R. Wayne Davies

  3. University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, 75390-9148, Texas, USA

    Raymond J. MacDonald

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  1. Nicola J. Craig
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  2. María B. Durán Alonso
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  3. Kim L. Hawker
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  4. Paul Shiels
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  7. Neil K. Bennett
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  8. Maurice Canham
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  9. Denise Donald
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  10. Mary Gardiner
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  11. Desmond P. Gilmore
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  12. Raymond J. MacDonald
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  13. Kirsty Maitland
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  14. Andrew S. McCallion
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  15. David Russell
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  16. Anthony P. Payne
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  17. Roger G. Sutcliffe
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  18. R. Wayne Davies
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Corresponding author

Correspondence to R. Wayne Davies.

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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

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