SEROTONERGIC GENE FUNCTION AND BEHAVIOR IN TRANSGENIC MICE

由于酒精中毒与5-羟色胺代谢减少有关，我们有 重点研究5-羟色胺能行为的遗传决定因素 导致酗酒倾向的因素。在神经元中， 在中缝核团中，5-羟色胺的生物合成受 色氨酸羟化酶(TPH)，它是限速的。这个 小鼠TPH基因及其编码基因已被克隆。这些 序列已与HSV胸苷激酶和 小鼠金属硫蛋白基因。这些都被引入了MICE 胚胎创造转基因小鼠以研究控制基因序列 组织特异性和发育性表达并表征效应 TPH基因活性高低与TPH表达细胞的消融 在行为上。

Since alcoholism is associated with decreased serotonin turnover, we have focused on genetic determinants of serotonergic behaviors to identify factors contributing to a predisposition to alcoholism. In neurons, of the raphe nuclei, serotonin biosynthesis is governed by the activity of the tryptophan hydroxylase (TPH) enzyme, which is rate-limiting. The cDNA and gene coding for murine TPH were previously cloned. These sequences have been combined with sequences from HSV thymidine Kinase and mouse metallothionein genes. These are being introduced into mouse embryos to create transgenic mice to study gene sequences controlling tissue-specific and developmental expression and to characterize effects of high and low TPH gene activity and ablation of TPH-expressing cells on behavior.