Animal models of human disease are important tools for revealing the underlying mechanisms of pathophysiology and developing therapeutic strategies. Several unique mouse calcium channel mutants have been identified with nonepileptic, episodic dyskinetic movements that are phenotypically similar to human paroxysmal dyskinesias. In this report, video demonstrations of these motor attacks are provided for two previously described mouse mutants, tottering and lethargic, as well as a new one, rocker. Semiquantitative comparisons using two different rating scales reveal differences in attack morphology, severity, and duration among the strains. These mice provide three independent models of paroxysmal dyskinesia and support for prior proposals that channelopathies may underlie the human disorders.
Keywordstottering; lethargic; rocker; paroxysmal dyskinesia; dystonia; channelopathyThe paroxysmal dyskinesias are a group of rare disorders characterized by intermittent attacks of involuntary abnormal movements.1 -3 These movements are often dystonic or choreiform, but may include a variety of other abnormalities. Unlike epilepsy, they are not associated with abnormal activity on electroencephalograms (EEGs).The paroxysmal dyskinesias are divided currently into three groups, which are based on the triggers of attacks, average attack duration, predominant morphology, and other features. [1][2][3] Paroxysmal nonkinesigenic dyskinesia is precipitated by stress, caffeine, or alcohol. The frequency of attacks ranges from a few per day to a few per year, with a duration of a few hours to several days. In contrast, attacks of paroxysmal kinesigenic dyskinesia are brought on by sudden movement, startle, and even passive manipulation of muscles. They are more frequent but shorter, occur many times per day, and last less than a few minutes each. In paroxysmal exertional dyskinesia, attacks are caused by prolonged exercise. Attacks are of intermediate duration with a frequency tied to the level of physical exertion.Recent studies also have revealed paroxysmal dyskinesias in certain strains of mice. The tottering mouse carries a mutation in the Cacna1a gene, which encodes a calcium channel subunit. 4,5 These mutants exhibit mild ataxia at baseline with intermittent attacks of severely disabling dyskinetic movements. 6,7 The lethargic mouse carries a mutation in the Cacnb4 gene, which encodes a different calcium channel subunit. 8 These mutants exhibit mild ataxia and a hypokinetic syndrome at baseline with intermittent attacks of dyskinetic movements. 9 The purpose of this report is to provide a video demonstration of the motor phenotypes of tottering and lethargic mice. In addition, we describe paroxysmal dyskinesia in a third mutant mouse, rocker, which also carries a mutation in the Cacna1a gene, but different from that in tottering
