Abstracts

Four genes, [italic]Bis1[/italic], [italic]Bis2[/italic], [italic]Bis3[/italic] and [italic]Bis4[/italic] have been identified for their involvement in beta-carboline-induced seizures in mice. These genes have been respectively mapped on chromosome 4, 13, 9 and 7 [1][sub]^.[/sub] [italic]Bis2[/italic] have been localized in a linkage-strain of mice C3XtEso bred in our colony and derived from C3HeB/FeJ [italic]Xt/+ Eso/+[/italic]. This strain is maintained with forced heterozygocity ([italic]Gli3[/italic][italic]^Xt-J[/italic][italic]/Gli3⁺[/italic] vs [italic]Gli3⁺/Gli3⁺[/italic]) for a small chromosomal fragment surrounding the [italic]Gli3[/italic] gene on chromosome 13. [italic]Gli3[/italic][italic]^Xt-J[/italic] is a mutated form for the [italic]Gli3[/italic] gene, coding for an extra digit on the pre-axial site of the limb. And it has been observed that the mutated mice [italic]Gli3[/italic][italic]^Xt-J[/italic][italic]/Gli3⁺[/italic] were significantly more resistant to the convulsive effect of a single injection of methyl-[beta]-carboline-3-carboxylate (beta-CCM - a beta-carboline) than the wild mice [italic]Gli3⁺/Gli3⁺[/italic]. This result has been interpreted as the influence of a polymorphic gene - named [italic]Bis2[/italic] - included in the heterozygous fragment surrounding and co-segregating with [italic]Gli3[/italic].
The genetic mechanism which underlies the reactivity to the beta-carbolines and those which controls spikes and waves discharges (SWD) characterizing absence epilepsy appear genetically dependent. Since [italic]Bis2[/italic] regulated the beta-CCM-induced seizure susceptibility, the question whether [italic]Bis2[/italic] would also be involved in SWD control and/or genesis was addressed in the present study. Two groups of C3XtEso male mice - [italic]Gli3[/italic][italic]^Xt-J[/italic][italic]/Gli3⁺[/italic] and [italic]Gli3⁺/Gli3⁺[/italic]- were formed. All animals were implanted under general anaesthesia (chloral hydrate, 400 mg/kg, i.p.) with five monopolar tungsten rod electrodes; four placed bilaterally over the frontal and parietal cortex and one placed over the cerebellum as reference electrode. Animals were allowed at least two weeks for recovery.
EEG activities were recorded in freely moving animals placed in a plexiglas cage placed in a Faraday cage. The mice were connected to the EEG apparatus with flexible wires and recorded for 40 minutes. Animals were continuously observed and the duration and number of seizures were evaluated. A significant difference was observed between [italic]Gli3[/italic][italic]^Xt-J[/italic][italic]/Gli3⁺[/italic] and [italic]Gli3⁺/Gli3⁺[/italic]as well as for SWD frequency (p[lt]0.0001) than for SWD cumulated duration (p[lt]0.0001). This result confirms the dependence between beta-CCM-induced seizure regulation and SWD activity previously observed. The next stage of this work will consist in a fine-mapping of the [italic]Bis2[/italic] gene.
[1] http://www.informatics.jax.org/searches/marker_form.shtml