Paroxysmal dyskinesias in the lethargic mouse mutant.
Lethargic mutant mice carry a mutation in the CCHB4 gene, which encodes the beta4 subunit of voltage-regulated calcium channels. These mutants have been shown to display a complex neurobehavioral phenotype that includes EEG discharges suggestive of absence epilepsy, chronic ataxia, and hypoactivity. The current studies demonstrate a fourth element of their phenotype, consisting of transient attacks of severe dyskinetic motor behavior. These attacks can be triggered by specific environmental and chemical influences, particularly those that stimulate locomotor activity. Behavioral and EEG analyses indicate that the attacks do not reflect motor epilepsy, but instead resemble a paroxysmal dyskinesia. The lethargic mutants provide additional evidence that calcium channelopathies can produce paroxysmal dyskinesias and provide a novel model for studying this unusual movement disorder.
Khan
Zubair
Z
Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 21287, USA.
Jinnah
H A
HA
D000367:Age Factors; D000818:Animals; D018726:Anti-Dyskinesia Agents / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D015220:Calcium Channels / Q000235:genetics; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002819:Chorea / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D015331:Cohort Studies; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D051379:Mice; D008818:Mice, Neurologic Mutants; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills; D010641:Phenotype; D021122:Protein Subunits; D012720:Severity of Illness Index; D012894:Sleep Stages / Q000235:genetics
D018726:Anti-Dyskinesia Agents; D000927:Anticonvulsants; D015220:Calcium Channels; D000697:Central Nervous System Stimulants; D021122:Protein Subunits