title: Quantitative trait locus on distal chromosome 1 regulates the occurrence of spontaneous spike-wave discharges in DBA/2 mice.
abstract: OBJECTIVE
  Most common forms of human epilepsy result from a complex combination of polygenetic and environmental factors. Quantitative trait locus (QTL) mapping is a first step toward the nonbiased discovery of epilepsy-related candidate genes. QTL studies of susceptibility to induced seizures in mouse strains have consistently converged on a distal region of chromosome 1 as a major phenotypic determinant; however, its influence on spontaneous epilepsy remains unclear. In the present study we characterized the influence of allelic variations within this QTL, termed Szs1, on the occurrence of spontaneous spike-wave discharges (SWDs) characteristic of absence seizures in DBA/2 (D2) mice.
  
  
  METHODS
  We analyzed SWD occurrence and patterns in freely behaving D2, C57BL/6 (B6) and the congenic strains D2.B6-Szs1 and B6.D2-Szs1.
  
  
  RESULTS
  We showed that congenic manipulation of the Szs1 locus drastically reduced the number and the duration of SWDs in D2.B6-Szs1 mice, which are homozygous for Szs1 from B6 strain on a D2 strain background. However, it failed to induce the full expression of SWDs in the reverse congenic animals B6.D2-Szs1.
  
  
  CONCLUSIONS
  Our results demonstrate that the occurrence of SWDs in D2 animals is under polygenic control and, therefore, the D2 and B6 strains might be a useful model to dissect the genetic determinants of polygenic SWDs characteristic of typical absence seizures. Furthermore, we point to the existence of epistatic interactions between at least one modifier gene within Szs1 and genes within unlinked QTLs in regulating the occurrence of spontaneous nonconvulsive forms of epilepsies.
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19106-6074, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bessaïh
authors.forename: Esther Garcia
authors.initials: EG
authors.lastname: de Yebenes
authors.forename: Kyle
authors.initials: K
authors.lastname: Kirkland
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Higley
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Buono
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Ferraro
authors.forename: Diego
authors.initials: D
authors.lastname: Contreras
mesh_terms: D000818:Animals; D020296:Animals, Congenic / Q000235:genetics; D001921:Brain / Q000503:physiopathology; D002874:Chromosome Mapping; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D040641:Quantitative Trait Loci / Q000235:genetics*