The autosomal dominant episodic movement disorder, paroxysmal nonkinesigenic dyskinesia (PKND), is associated with two valine to alanine substitutions in the uncharacterized human gene, PNKD. This transgenic strain, mut Tg (line 671), expresses the long isoform of the Pnkd gene and the A7V and A9V substitutions. The long isoform of PNKD is expressed only in the central nervous system. In humans, PNKD movement disorder is observed following stress, caffeine or alcohol intake. Mice carrying the transgene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Following i.p. administration of ethanol or caffeine, transgenic mice exhibit nigrostriatal neurotransmission deficits, reduced extracellular dopamine levels in the striatum, an increased percentage of striatal dopamine release, and dyskinesia characterized by severe axial stiffness and abnormal limb movements. Non-induced mice exhibit lower glutathione levels in the frontal cortex. This mutant mouse strain may be useful in studies of autosomal dominant episodic movement disorder (PKND) and cellular redox regulation. No discernible phenotypic differences have been observed between transgenic line 671 which carries an estimated single copy of the transgene and line 704 (see Stock No. 022146) which carries approximately 2 copies.
