Mouse models of spike-wave epilepsy

The mouse is a well-established model for human genetic disorders. An incre asing number of single-gene human diseases are being elucidated through the use of mouse models. Recently genes for three of the six well-characterise d single locus models for human spike-wave epilepsy have been isolated and published. The tottering mouse has been shown to be due to mutations in the gene encoding the high voltage-activated alpha 1(A) calcium channel subuni t. The lethargic mouse has been shown to be due to mutations in the gene en coding another calcium channel subunit, beta 4. The slow-wave epilepsy mous e phenotype is the result of loss of function of the ubiquitous sodium hydr ogen exchanger NHEI. These genes and the pathways they are involved in are now candidates for human spike-wave epilepsy. The six mouse models and thos e genes underlying the spike-wave phenotype are discussed in conjunction wi th how these mutations were discovered and how they may give rise to the se izure phenotypes. Several nonepilepsy human neurologic disorders have been shown to be allelic with the tottering mouse. The question this raises as t o the validity of these models for human spike-wave epilepsy is considered. Finally, the effect these discoveries will have on the understanding and t reatment of human spike-wave epilepsy are discussed.