Rocker is a new variant of the voltage-dependent calcium channel gene Cacna1a

Rocker (gene symbol rkr), a new neurological mutant phenotype, was found in descendents of a chemically mutagenized male mouse. Mutant mice display an ataxic, unstable gait accompanied by an intention tremor, typical of cereb ellar dysfunction. These mice are fertile and appear to have a normal life span. Segregation analysis reveals rocker to be an autosomal recessive trai t. The overall cytoarchitecture of the young adult brain appears normal, in cluding its gross cerebellar morphology. Golgi-Cox staining, however, revea ls dendritic abnormalities in the mature cerebellar cortex characterized by a reduction of branching in the Purkinje cell dendritic arbor and a "weepi ng willow" appearance of the secondary branches. Using simple sequence leng th polymorphism markers, the rocker locus was mapped to mouse chromosome 8 within 2 centimorgans of the calcium channel alpha 1a subunit (Cacna1a, for merly known as tottering) locus. Complementation tests with the leaner muta nt allele (Cacna1a(la)) produced mutant animals, thus identifying rocker as a new allele of Cacna1a (Cacna1a(rkr)). Sequence analysis of the cDNA reve aled rocker to be a point mutation resulting in an amino acid exchange: T13 10K between transmembrane regions 5 and 6 in the third homologous domain. I mportant distinctions between rocker and the previously characterized allel es of this locus include the absence of aberrant tyrosine hydroxylase expre ssion in Purkinje cells and the separation of the absence seizures (spike/w ave type discharges) from the paroxysmal dyskinesia phenotype. Overall thes e findings point to an important dissociation between the seizure phenotype s and the abnormalities in catecholamine metabolism, and they emphasize the value of allelic series in the study of gene function.