Mapping of two genes that influence susceptibility to audiogenic seizures in crosses of C57BL/6J and DBA/2J mice

Abstract

The difference in susceptibility to audiogenic seizures (AGS) between C57BL/6J and DBA/2J inbred strains of mice is due to multiple genetic factors. AGS susceptibility was tested in 21-day-old mice from classical crosses, BXD recombinant inbred (RI) strains, a congenic DBA/2N.B6N-Ah ^b inbred strain and crosses between the BXD RI strains and DBA/2J. Analysis of these data reveals that the variation in AGS susceptibility between these two strains results from allelic differences at three or more loci. Most of the variation is due to allelic differences at two loci. The first,Asp-1 (formerlyIas), is a major gene located on chromosome 12, betweenAh andD12 Nyul. The second,Asp-2 (formerlyasp), is a minor gene located on chromosome 4, tightly linked tob. The negative correlation of brain stem Ca²⁺-ATPase activity and AGS susceptibility in the BXD RI strains suggests that the strain difference in Ca²⁺-ATPase activity is inherited as a polygenic trait and thatAsp-1 andAsp-2 are linked to, or identical to, factors that influence Ca²⁺-ATPase activity.