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Sleep. 2007 Feb;30(2):169-76.

Sleep-related epilepsy in the A/J mouse.

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1
Department of Medicine, Case Western Reserve University, Cleveland OH, USA. kps@po.cwru.edu

Abstract

RATIONALE:

Evident seizures during sleep are common in clinical practice but are uncommonly considered in animal models of epilepsy. A previous observation of spontaneous spike-and-wave activity during sleep in several A/J mice (A/J JAX) from Jackson Laboratory (Bar Harbor, ME) prompted this description of the inheritance of epileptic activity.

METHODS:

Mice from A/J, C57BI/6J (B6), and chromosomal substitutions strains were instrumented to record EEG and EMG activity over time without and with anti-epileptic drugs. Intercrosses were performed using linkage analysis to localize sub-chromosomal regions.

RESULTS:

Spike-discharge patterns (n = 12 mice) were of average duration of 1.9 seconds at a rate per hour of 17, with an intrinsic frequency of 6.41 Hz and an amplitude of 634.8 microV. Clonic movements were observed in < 10% of the episodes. Episodes were expressed (> 75%) either in slow-wave sleep or in transitions to and from slow-wave sleep. Events were rare in paradoxical sleep. Compared with vehicle, intraperitoneal administration of ethosuximide (150 mg/kg) or diazepam (5 mg/kg) inhibited or eliminated seizure activity, respectively. In contrast, spontaneous spike-and-wave activity was not observed in A/J mice from Harlan National Laboratories (Indianapolis, Ind) or in B6 mice from Jackson Laboratory. In an intercross between A/J JAX and B6 mice, the trait was not present in the first generation. The trait was observed in 2 chromosome-substitution strains, B6.A4 and B6.A7. In the intercross second generation of these chromosome-substitution strains (n = 113), significant linkage was observed to loci on chromosome 4.

CONCLUSIONS:

This is a sleep-related epilepsy phenotype that exhibits an oligogenic pattern of allelic inheritance.

PMID:
17326542
[Indexed for MEDLINE]
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