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。在拉斐尔 5-羟色胺的生物合成是由神经元的活性控制的 色氨酸羟化酶(TPH)，这是限速的。CDNA3 编码小鼠TPH的基因已被克隆。这些序列 已经与单纯疱疹病毒胸苷激酶和小鼠的序列结合 金属硫蛋白基因。这些细胞被引入小鼠胚胎中，以 创造转基因小鼠来研究控制组织的基因序列- 特异性和发育性表达，并表征其影响 TPH基因的高、低活性及TPH表达细胞在体外的消融 行为。

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 the raphe neurons, 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.