Murphy Dennis L, Lesch Klaus-Peter
Laboratory of Clinical Science, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Rev Neurosci. 2008 Feb;9(2):85-96. doi: 10.1038/nrn2284.
Mutations resulting in reduced or completely abrogated serotonin-transporter (SERT) function in mice have led to the identification of more than 50 different phenotypic changes, ranging from increased anxiety and stress-related behaviours to gut dysfunction, bone weakness and late-onset obesity with metabolic syndrome. These multiple effects, which can be amplified by gene-environment and gene-gene interactions, are primarily attributable to altered intracellular and extracellular serotonin concentrations during development and adulthood. Much of the human data relating to altered expression of the gene that encodes SERT are based on genetic-association findings or correlations and are therefore not as robust as the experimental mouse results. Nevertheless, SERT-function-modifying gene variants in humans apparently produce many phenotypes that are similar to those that manifest themselves in mice.
导致小鼠血清素转运体（SERT）功能降低或完全丧失的突变已促使人们识别出50多种不同的表型变化，范围从焦虑增加和应激相关行为到肠道功能障碍、骨骼脆弱以及伴有代谢综合征的迟发性肥胖。这些多重效应可因基因-环境和基因-基因相互作用而放大，主要归因于发育和成年期细胞内和细胞外血清素浓度的改变。许多与编码SERT的基因表达改变相关的人类数据基于遗传关联研究结果或相关性，因此不如实验小鼠结果可靠。尽管如此，人类中改变SERT功能的基因变体显然会产生许多与小鼠中表现出的表型相似的表型。
