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

Abstract

Rats harboring the <i>agu</i> 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 <i>kinase Cγ</i> (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