Mapping loci for pentylenetetrazol-induced seizure susceptibility in mice

DBA/2J (D2) and C57BL/6J (B6) mice exhibit differential sensitivity to seiz ures induced by various chemical and physical methods, with D2 mice being r elatively sensitive and B6 mice relatively resistant. We conducted studies in mature D2, B6, Fl, and F2 intercross mice to investigate behavioral seiz ure responses to pentylenetetrazol (PTZ) and to map the location of genes t hat influence this trait. Mice were injected with PTZ and observed for 45 m in. Seizure parameters included latencies to focal clonus, generalized clon us, and maximal seizure. Latencies were used to calculate a seizure score t hat was used for quantitative mapping. F2 mice (n = 511) exhibited a wide r ange of latencies with two-thirds of the group expressing maximal seizure. Complementary statistical analyses identified loci on proximal (near D1Mit1 1) and distal chromosome 1 (near D1Mit17) as having the strongest and most significant effects in this model. Another locus of significant effect was detected on chromosome 5 (near D5Mit398). Suggestive evidence for additiona l PTZ seizure-related loci was detected on chromosomes 3, 4, and 6. Of the seizure-related loci identified in this study, those on chromosomes 1 (dist al), 4, and 5 map close to loci previously identified in a similar F2 popul ation tested with kainic acid. Results document that the complex genetic in fluences controlling seizure response in B6 and D2 mice are partially indep endent of the nature of the chemoconvulsant stimulus with a locus on distal chromosome 1 being of fundamental importance.