SEROTONERGIC GENE FUNCTION AND BEHAVIOR IN TRANSGENIC MICE

由于酒精中毒与血清素周转减少有关，我们 专注于研究多巴胺能行为的遗传决定因素， 导致酗酒倾向的因素。 在中缝 在神经元中，5-羟色胺的生物合成受神经元的活性控制。 色氨酸羟化酶（TPH），这是限速酶。 的cdna 和编码鼠TPH的基因已被克隆。 这些序列 已经与来自HSV胸苷激酶和小鼠 金属硫蛋白基因 它们被引入小鼠胚胎中， 制造转基因小鼠来研究控制组织的基因序列- 具体和发展的表达，并表征影响 高和低TPH基因活性，以及TPH表达细胞的消融， 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.