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

  • G. K. Kostopoulos
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 35)


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.


Locus Coeruleus Mossy Fiber Absence Seizure Generalize Epilepsy Motor Seizure 
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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • G. K. Kostopoulos
    • 1
  1. 1.Department of PhysiologyUniversity of Patras Medical SchoolPatrasGreece

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