The tottering mouse: a critical review of its usefulness in the study of the neuronal mechanisms underlying epilepsy

Summary

The tottering mouse resulted from a recessively inherited, autosomal, single-locus mutation which produces a very characteristic neurological and cellular phenotype. Almost simultaneously and late in the development of this mutant appears a triad of symptoms: frequent episodes of absence seizures with spike-and-wave discharges; more rarely occurring episodes of focal motor seizures; and ataxia. Electrographic, behavioural and pharmacological similarities to absence epilepsy in man make the tottering mouse a useful animal model for testing new anti-absence drugs. It also affords a unique opportunity to study the effects of multiple alleles on epileptic behaviour. The neuronal mechanisms underlying the generation of absence seizures in this mutant are apparently a combination of a generalized noradrenergic hyperactivity in the brain and some gene-linked, but unknown, conditions prevailing in an earlier phase of development at specific brain areas which induce the generalized forebrain hyper-innervation by locus coeruleus terminals Several biochemically, microscopically and electrophysiologically identified cellular differences between normal and tottering mice are potential aspects of this primary developmental defect. Research into these gene-linked neuronal characteristics co-inherited with seizures in this mutant makes the tottering mouse a powerful tool in the study of cellular mechanisms underlying genetically determined factors in epileptogenesis.