Chemoconvulsant-induced seizure susceptibility: Toward a common genetic basis?

Despite the efforts employed, understanding the genetic architecture underlying epilepsy remains difficult. To reach this aim, convulsive epilepsies are classically modeled in mice, where genetic studies are less constricting than in humans. Pharmacogenetic approaches are one major source of investigation where kainic acid, pentylenetetrazol, and the ß-carboline family represent compounds that are used extensively. Several quantitative trait loci (QTLs) influencing the convulsant effects of these drugs have been mapped using either recombinant inbred strains (RIS) or segregating F2 populations (or both). In our laboratory, we have recently mapped two QTLs for methyl 6, 7-dimethoxy-4-ethyl-ß-carboline-3-carboxylate (DMCM), and seizure response using an F2 method. One is located on the distal part of Chromosome 1, a region implicated in a number of other studies. Here, we address the general importance of this chromosomal fragment for influencing seizure susceptibility.