title: Sleep-related epilepsy in the A/J mouse.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland OH, USA. kps@po.cwru.edu
authors.forename: Kingman P
authors.initials: KP
authors.lastname: Strohl
authors.forename: Laura
authors.initials: L
authors.lastname: Gallaugher
authors.forename: Audrey
authors.initials: A
authors.lastname: Lynn
authors.forename: Lee
authors.initials: L
authors.lastname: Friedman
authors.forename: Annie
authors.initials: A
authors.lastname: Hill
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Singer
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Joseph
authors.initials: J
authors.lastname: Nadeau
mesh_terms: D000483:Alleles; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D033481:Chromosomes, Mammalian / Q000235:genetics; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004569:Electroencephalography; D004576:Electromyography / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D005013:Ethosuximide / Q000627:therapeutic use; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D012890:Sleep / Q000502:physiology*
chemical_list: D000927:Anticonvulsants; D005013:Ethosuximide; D003975:Diazepam