Maoa c.1409 T>C同义突变小鼠情绪的雌雄差异研究
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1.国家烟草质量监督检验中心;2.中国科学技术大学

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省部级重点科技项目(110202101018(XX-04);110202102014)


A study on the differences in emotional behavior between males and women in mice with Maoa c.1409 T>C synonymous mutants
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1.CTQTC;2.USTC

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Funded by Provincial and Ministerial Key Science and Technology Projects (110202101018 (XX-04); 110202102014)

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    摘要:

    目的:探究单胺氧化酶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影响。方法:本研究利用CRISPR/Cas9技术构建SNP同义突变小鼠模型,模拟人群中rs11370770位点的C和T等位基因多态性,通过动物模型的动物行为学和基因表达水平评价该基因的雌雄差异影响。动物行为学方面主要通过旷场实验(Open field test,OFT)、高架十字迷宫(Elevated plus maze,EPM)、防御性掩埋(Defensive burial experiment,DBE)、3D行为学分析(3D behavioral analysis)等方法评估Maoa同义突变基因多态性造成的雌雄行为学差异;基因表达方面检测小鼠MAOA含量和酶活性,评估Maoa rs1137070位点多态性对雌雄SNP小鼠基因表达的影响。结果:旷场实验结果表明,雌性SNP小鼠在旷场中中心区域的停留时间明显高于雄性SNP小鼠(P<0.001);高架十字迷宫实验结果表明雄性SNP小鼠进入开放臂时间和次数高于雌性SNP小鼠,但无显著差异;防御性掩埋实验结果表明,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)。三维精细行为分析发现除小鼠运动轨迹和攀爬行为外无显著雌雄差异性。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小鼠酶活性无显著差异。结论:MAOA c.1409 T>C的同义突变可能通过影响雌雄SNP小鼠的MAOA表达情况引起雌雄小鼠恐惧和焦虑和情绪差异性。

    Abstract:

    Objective: To investigate the effect of 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 SNP synonymous mutation, which simulated the C and T allele polymorphisms of rs11370770 in the population, and evaluated the differential effect of this gene on male and female differences through animal behavior and gene expression levels in animal models. In terms of animal behavior, open field test (OFT), elevated plus maze (EPM), defensive burial experiment (DBE), and 3D behavioral analysis were mainly used analysis) and other methods were used to evaluate the behavioral differences between male and female males caused by polymorphisms in Maoa synonymous mutant genes, and the MAOA content and enzyme activity in mice were detected to evaluate the effect of Maoa rs1137070 polymorphisms on gene expression in male and female SNP mice. Results: The results of the open field experiment showed that the residence time of female SNP mice in the central area of the open field was significantly higher than that of male SNP mice (P<0.001), the results of elevated cross maze experiment 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, and the results of defensive burial test showed that the number and duration of excavation of female SNP mice were significantly reduced to the threat of rat urine (P<0.01). Three-dimensional fine behavior analysis showed that there was no significant male and female difference except for the movement trajectory and climbing behavior of mice. Compared with male SNP 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. Conclusion: The synonymous mutation of MAOA c.1409 T>C may cause fear, anxiety and mood differences in male and female mice by affecting the expression of MAOA in male and female SNP mice.

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  • 收稿日期:2024-03-14
  • 最后修改日期:2024-04-28
  • 录用日期:2024-10-16
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