中枢神经元中SEL1L基因缺失对小鼠行为学的影响
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苏州大学特聘教授启动经费(编号:Q421600114)。


Impact of SEL1L deletion in central nervous system on the behavior of mice
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    摘要:

    目的 探究内质网蛋白SEL1L在维持哺乳动物中枢神经系统正常生理活动中的作用。方法 利用Cre/loxp技术,构建神经元(neuron)特异性SEL1L基因敲除小鼠(NKO),按照不同性别分为实验组(NKO)与野生型组(WT),每组10只。比较分析小鼠在出生后不同日龄的存活时间、体重及抓力、平衡协调性、运动、焦虑情绪等行为学指标等差异,对SEL1L在中枢神经系统中的生理功能做出判断。结果 NKO小鼠存活时间为(6±3)周;其体重在第3周、第5周、第8周分别为WT小鼠的54.64%、40.54%、38.57%;NKO雄性小鼠的抓力在第3、5、8周分别为WT雄性小鼠的44.24%、48.09%、49.04%,NKO雌性小鼠为WT雌性小鼠的39.39%、50.19%、49.69%;第3、5、8周的NKO雄性小鼠的平衡协调性反应出的运动时间分别为WT小鼠的26.92%、41.58%、37.48%,NKO雌性小鼠为WT小鼠的46.02%、47.67%、38.48%;第3、5、8周的NKO雄性小鼠在旷场实验中运动路程、进入中心区域时间分别为WT小鼠的(24.63%,9.57%)、(25.87%,11.63%)、(51.96%、9.97%),NKO雌性小鼠为WT小鼠的(35.62%,25.93%)、(42.75%,9.77%)、(34.77%,14.49%),且表现出明显的焦虑情绪。差异有显著性(P< 0.001)。结论 NKO小鼠在存活时间、体重、平衡协调性、运动、焦虑情绪等行为学指标等方面都明显差于野生型小鼠,说明SEL1L蛋白在维持中枢神经正常功能中是必须的。

    Abstract:

    Objective To investigate the role of endoplasmic reticulum protein SEL1L in the maintenance of physiological activities of the central nervous system in mammals. Methods Neuron-specific SEL1L knockout mice (NKO) were generated using the Cre/loxp strategy. Both female and male mice were divided into experimental group (NKO) and wild-type group (WT), with 10 mice in each group and of both sexes. The postnatal survival time, body weight and behavioral indicators such as strength of skeletal muscle, balance coordination, locomotion and anxiety of the mice in each group were compared and analyzed to evaluate the physiological role of SEL1L in the central nervous system. Results The survival time of the NKO mice was only (6±3) weeks on average. Although the neonatal body weight of the NKO mice was similar to that of the wild-type mice, both the male and female NKO mice were significantly more retarded in growth than the wild-type mice, since the body weight of the NKO mice was 54.64%, 40.54% and 38.57% of the WT mice at 3, 5 and 8 weeks of age, respectively. The strength of skeletal muscle of the male NKO mice was 44.24%, 48.09% and 49.04% of male WT mice, and as for the female NKO mice, it was 39.39%, 50.19% and 49.69% of the female WT mice at those three postnatal time points. The movement time, which indicates the balance coordination, of the male NKO mice was 26.92%, 41.58% and 37.48% of the male WT mice, and the movement time of the female NKO mice was 46.02%, 47.67% and 38.48% of the female WT mice. The movement distance in the open field test and the time spent to enter the central region of the male NKO mice were (24.63%, 9.57%), (25.87%, 11.63%) and (51.96%, 9.97%) of the male WT mice, and as for the female NKO mice, those two indicators were (35.62%, 25.93%), (42.75%, 9.77%) and (34.77%, 14.49%) of the female WT mice. In addition, the NKO mice showed more prominent anxiety. There were significant differences between the NKO group and the WT group for all of the experiments above (P < 0.001). Conclusions The data of the postnatal survival time, the body weight and the behavioral indicators such as balance coordination, locomotion and anxiety of the mice show that the condition of the NKO mice is significantly worse than that of the WT mice, indicating an important role of SEL1L in the maintenance of physiological functions of the central nervous system.

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王婧怡,刘青青,潘志雄,周正宇,龙乔明.中枢神经元中SEL1L基因缺失对小鼠行为学的影响[J].中国比较医学杂志,2017,27(9):53~59.

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  • 收稿日期:2017-01-16
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  • 在线发布日期: 2017-09-23
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