Martin B, Clément Y, Venault P, Chapouthier G
Génétique, Neurogénétique et Comportement, URA 1294-CNRS, Paris, France.
J Hered. 1995 Jul-Aug;86(4):274-9. doi: 10.1093/oxfordjournals.jhered.a111581.
beta-Carbolines, such as methyl beta-carboline-3-carboxylate (beta-CCM), attach to the benzodiazepine receptors in the brain, but have effects completely opposite to those of benzodiazepines: beta-CCM is a convulsant at high doses, an anxiogenic at moderate doses, and enhances learning at low doses. The aim of this work was to detect some of the chromosomal segments involved in the regulation of beta-CCM-induced seizures. The method used was a derivation of the classical use of linkage-testing strains. We tested several strains and some of their intercrosses and back-crosses. For two of these strains, we obtained significant results showing that genes located on chromosomes 4 and 13, provisionally termed respectively Bis1 and Bis2, were involved in the regulation of beta-carboline-induced seizures. Testing of these two strains with two other convulsant agents (pentylenetetrazol, which acts at the picrotoxine site of the GABA receptor complex, and strychnine, which acts at the glycinergic receptor) provided evidence that the genes implicated are not involved in general seizure processes but specifically in beta-CCM-induced seizures.
β-咔啉类化合物，如β-咔啉-3-羧酸甲酯（β-CCM），可与大脑中的苯二氮䓬受体结合，但其作用与苯二氮䓬类药物完全相反：高剂量时β-CCM是一种惊厥剂，中等剂量时是一种致焦虑剂，低剂量时可增强学习能力。这项工作的目的是检测参与β-CCM诱导癫痫发作调节的一些染色体片段。所采用的方法是对经典连锁测试菌株使用方法的一种衍生。我们测试了几种菌株及其一些杂交和回交后代。对于其中两个菌株，我们获得了显著结果，表明位于4号和13号染色体上的基因，暂分别命名为Bis1和Bis2，参与了β-咔啉诱导癫痫发作的调节。用另外两种惊厥剂（戊四氮，作用于GABA受体复合物的印防己毒素位点；士的宁，作用于甘氨酸能受体）对这两个菌株进行测试，结果表明所涉及的基因并非参与一般的癫痫发作过程，而是特异性地参与β-CCM诱导的癫痫发作。
