title: Audiogenic seizure proneness requires the contribution of two susceptibility loci in mice.
abstract: Juvenile mice of the DBA/2J strain undergo generalised seizures when exposed to a high-intensity auditory stimulus. Genetic analysis identified three different loci underlying this audiogenic seizure proneness (ASP)-Asp1, Asp2 and Asp3 on chromosomes 12, 4 and 7, respectively. Asp1 is thought to have the strongest influence, and mice with only Asp1 derived from the DBA/2J strain are reported to exhibit ASP. The aim of this study was to characterise more accurately the contributions of the Asp1 and Asp3 loci in ASP using congenic strains. Each congenic strain contains a DBA/2J-derived interval encompassing either Asp1 or Asp3 on a C57BL/6J genetic background. A double congenic C57BL/6J strain containing both Asp loci derived from DBA/2J was also generated. Here, we report that DBA/2J alleles at both of these Asp loci are required to confer ASP because congenic C57BL/6 mice harbouring DBA/2J alleles at only Asp1 or Asp3 do not exhibit ASP, whereas DBA/2J alleles at both loci resulted in increased susceptibility for audiogenic seizure in double congenic C57BL/6 mice.
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: M Catharine
authors.initials: MC
authors.lastname: Jawahar
authors.forename: Carolina I
authors.initials: CI
authors.lastname: Sari
authors.forename: Yvette M
authors.initials: YM
authors.lastname: Wilson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodnicki
authors.forename: Mark
authors.initials: M
authors.lastname: Murphy
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D003433:Crosses, Genetic; D020195:Epilepsy, Reflex / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA