Gozes I, Glowa J, Brenneman D E, McCune S K, Lee E, Westphal H
Department of Chemical Pathology, Sackler School of Medicine, Tel Aviv University, Israel.
J Mol Neurosci. 1993 Fall;4(3):185-93. doi: 10.1007/BF02782501.
The molecular mechanisms responsible for behavior are largely unknown. A state of the art model, paving the path from genes to behavior, is offered by transgenic animals. Candidate molecules are classic neuropeptides, such as vasoactive intestinal peptide (VIP). Transgenic mice harboring a chimeric VIP gene driven by the polyoma promoter were produced. Behavioral studies revealed learning impairment and prolonged retardation in memory acquisition in the genetically altered animals. Furthermore, reduced performance was observed when the male transgenic mice were tested for sexual activity in the presence of receptive females. Surprisingly, radioimmunoassays showed an approx 20% decrease in the VIP content of the transgenic mice brains. To directly assess genetically reduced VIP content as a cause for learning impairment, transgenic mice carrying diphtheria toxin-encoding sequences driven by the rat VIP promoter were created. These animals had reduced brain VIP and exhibited deficiencies in learning abilities, strongly supporting an important neurobiological function for VIP in vivo.
行为背后的分子机制在很大程度上尚不清楚。转基因动物提供了一种先进的模型，为从基因到行为的研究铺平了道路。候选分子是经典的神经肽，如血管活性肠肽（VIP）。构建了携带由多瘤病毒启动子驱动的嵌合VIP基因的转基因小鼠。行为研究显示，基因改变的动物存在学习障碍以及记忆获取延迟延长的情况。此外，当对雄性转基因小鼠在有发情雌性存在的情况下进行性活动测试时，观察到其表现下降。令人惊讶的是，放射免疫分析显示转基因小鼠大脑中的VIP含量约减少了20%。为了直接评估基因导致的VIP含量降低是否是学习障碍的原因，构建了携带由大鼠VIP启动子驱动的编码白喉毒素序列的转基因小鼠。这些动物的大脑VIP减少，并表现出学习能力缺陷，有力地支持了VIP在体内具有重要神经生物学功能的观点。
