Allelic Variation of Human Serotonin Transporter Gene Expression
Allelic Variation of Human Serotonin Transporter Gene Expression
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DOI：
10.1046/j.1471-4159.1996.66062621.x
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发表时间：
1996-06
影响因子：
4.7
通讯作者：
A. Heils;A. Teufel;S. Petri;G. Stöber;P. Riederer;D. Bengel;K. Lesch
中科院分区：
文献类型：
--
作者：
A. Heils;A. Teufel;S. Petri;G. Stöber;P. Riederer;D. Bengel;K. Lesch
摘要：情绪、情感、认知和运动功能以及昼夜节律和神经内分泌节律，包括食物摄入、睡眠和生殖活动，都受到中脑中缝5-羟色胺（5-HT）系统的调节。通过指导突触后反应的幅度和持续时间，载体促进的5-HT转运进入突触前神经元和从突触前神经元释放对于突触能神经传递的微调至关重要。对环境因素、疾病和治疗诱导的5-HT转运蛋白（5-HTT）功能改变及其对早期脑发育、事件相关突触可塑性和神经退行性的影响的机制的兴趣广泛且日益增强。我们最近对人和鼠的5-HTT基因进行了表征，并对其5′-侧翼调控区进行了功能分析。与人5-HTT基因的转录装置相关的串联重复序列显示复杂的二级结构，抑制非多巴胺能神经元细胞中的启动子活性，并含有正调控成分。我们现在报告了这种重复元件的一种新的多态性，并为等位基因依赖性差异5-HTT启动子活性提供了证据。5-HTT相关功能的等位基因变异可能在复杂性状和行为的表达和调节中发挥作用。
Abstract: Mood, emotion, cognition, and motor functions as well as circadian and neuroendocrine rhythms, including food intake, sleep, and reproductive activity, are modulated by the midbrain raphe serotonin (5‐HT) system. By directing the magnitude and duration of postsynaptic responses, carrier‐facilitated 5‐HT transport into and release from the presynaptic neuron are essential for the fine tuning of serotonergic neurotransmission. Interest in the mechanism of environmental factor‐, disease‐, and therapy‐induced modification of 5‐HT transporter (5‐HTT) function and its impact on early brain development, event‐related synaptic plasticity, and neurodegeneration is widespread and intensifying. We have recently characterized the human and murine 5‐HTT genes and performed functional analyses of their 5′‐flanking regulatory regions. A tandemly repeated sequence associated with the transcriptional apparatus of the human 5‐HTT gene displays a complex secondary structure, represses promoter activity in nonserotonergic neuronal cells, and contains positive regulatory components. We now report a novel polymorphism of this repetitive element and provide evidence for allele‐dependent differential 5‐HTT promoter activity. Allelic variation in 5‐HTT‐related functions may play a role in the expression and modulation of complex traits and behavior.