Maoa c.1409 T>C同义突变小鼠情绪的雌雄差异研究  

Differences in emotional behavior between male and female mice with Maoa c.1409 T>C synonymous mutation

作　　者：李凯欣 刘光林 原茜倩 刘方邻[3] 陈欢[1] 侯宏卫[1] LI Kaixin;LIU Guanglin;YUAN Qianqian;LIU Fanglin;CHEN Huan;HOU Hongwei(China Tobacco Quality Supervision and Test Center,Key Laboratory of Tobacco Biological Effects,Joint Laboratory of Translational Neurobiology,Zhengzhou 450000,China;University of Science and Technology of China,Hefei 230026,China;Chinese Academy of SciencesHefei Institutes of Physical Science,Chinese Academy of Sciences,Heifei 230026,China)

机构地区：[1]国家烟草质量监督检验中心,烟草生物学效应重点实验室,转化神经生物学联合实验室,郑州450000 [2]中国科学技术大学,合肥230026 [3]中国科学院合肥物质科学研究院,合肥230026

出　　处：《中国实验动物学报》2024年第10期1295-1306,共12页Acta Laboratorium Animalis Scientia Sinica

基　　金：省部级重点科技项目(110202101018(XX-04),110202102014)。

摘　　要：目的探究单胺氧化酶A(monoamine oxidase A,MAOA),Maoa c.1409 T>C同义突变对小鼠焦虑、恐惧等情绪行为的雌雄差异。方法本研究利用CRISPR/Cas9技术构建基因多态性(single nucleotide polymorphism,SNP)同义突变小鼠模型,通过旷场实验(open field test,OFT)、高架十字迷宫(elevated plus maze,EPM)、防御性掩埋(defensive burial experiment,DBE)、强迫游泳(forced swimming test,FST)、3D行为学分析(3D behavioral analysis system,3D-AI)等方法评估雌雄行为学差异;并检测小鼠的MAOA含量和酶活性。结果OFT结果表明,雌性SNP小鼠在旷场中心区域的停留时间明显高于雄性SNP小鼠(P<0.001);EPM结果表明雄性SNP小鼠进入开放臂时间和次数高于雌性SNP小鼠,但无显著性差异;DBE结果表明,雌性SNP小鼠对于大鼠尿液的威胁其挖掘次数和挖掘持续时间显著下降(P<0.01);FST表明SNP雌鼠的不动时间更短,游泳时间更长(P<0.05),SNP小鼠表现出更显著的抑郁样行为,3D-AI发现雌雄小鼠在活动性以及攀爬转身奔跑动作方面有显著性差异(P<0.05)。Maoa检测发现与雄性SNP小鼠相比,雌性SNP小鼠的MAOA酶含量显著低于雄性SNP小鼠(P<0.001),但是雌雄SNP小鼠酶活性无显著性差异。结论Maoa c.1409 T>C的同义突变导致雌雄SNP小鼠的Maoa基因表达并引起小鼠焦虑、抑郁、恐惧情绪差异。Objective To investigate the effect of the monoamine oxidase A(MAOA),Maoa c.1409 T>C synonymous mutation on anxiety,fear,and other emotional behaviors in mice.Methods In this study,CRISPR/Cas9 technology was used to construct a mouse model of a single nucleotide polymorphism(SNP)synonymous mutation.We evaluated the differential effect of this gene between males and females through animal behavior and gene expression studies in animal models.In terms of animal behavior,an open field test,elevated plus maze test,defensive burial experiment,forced swimming test,and 3D behavioral analysis were used.Other method were used to evaluate behavioral differences between male and female mice with polymorphisms in Maoa synonymous mutant genes.Results The result of the open field experiment showed that the residence time of female SNP mice in the central area was significantly higher than that of male SNP mice(P<0.001).In the elevated cross maze experiment,the EPM result showed that the time and frequency of male SNP mice entering the open arm were higher than those of female SNP mice,but there was no significant difference.The defensive burial test showed that the number and duration of excavations by female SNP mice in response to rat urine were significantly reduced(P<0.01).The FST showed that SNP females had shorter immobility time and longer swimming time(P<0.05),and thus their depression was lower than males.3D-AI fine behavior analysis showed no significant male and female differences,except for the movement trajectory and climbing behavior of mice.The MAOA enzyme content of female SNP mice was significantly lower than that of male SNP mice(P<0.001),but there was no significant difference in enzyme activity between male and female SNP mice.Conclusions The synonymous mutation of Maoa c.1409 T>C acts by affecting the expression of MAOA and may have different fear,anxiety,and mood effects in male and female SNP mice.

关 键 词：单胺氧化酶A rs1137070 雌雄差异 行为学评价 

分 类 号：Q95-33[生物学—动物学]