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白细胞介素15受体α基因敲除小鼠的类精神 疾病行为分析
贺毅 杨健 贾立娜 马超 刘鑫垚 孙作厘
()
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目的 研究白细胞介素 15 受体 α(IL-15Rα)基因敲除对小鼠类精神疾病行为的影 响。方法 将 8 周龄的基因敲除小鼠分为纯合子和杂合子组,并以野生型小鼠作为对照,采用聚 合酶链反应(PCR)进行小鼠基因型鉴定,通过筑巢实验、社会交互实验及糖水偏好实验分析 IL- 15Rα 基因敲除小鼠的类精神疾病行为。结果 PCR 实验显示,野生型条带为 171 bp,纯合子条 带 为 280 bp,杂 合 子 条 带 为 171 bp 和 280 bp。 本 研 究 共 纳 入 8 只 野 生 型、14 只 杂 合 子 和 12 只 纯 合子进行行为学检测。(1)筑巢评分:与野生型相比,纯合子小鼠表现出明显的筑巢功能障碍,筑 巢评分[(1.58±0.79)分]显著低于野生型小鼠[(2.71±0.95)分,P< 0.05],杂合子小鼠的筑巢评分 [(2.21±1.05)分]介于野生型和纯合子小鼠之间,与野生型及纯合子型小鼠比较,差异均无统计学意 义(均P>0.05)。(2)三箱社交实验:纯合子小鼠在陌生小鼠所在箱中的运动距离和运动时间与空笼相比 差异均无统计学意义[运动距离:(22 395±8 664)mm比(18 057±3 438)mm;运动时间:(178.5±49.05) s 比 (161.1±49.84)s;t值分别为 1.612、0.865,均P> 0.05];杂合子小鼠在陌生小鼠所在箱中运动距离明 显长于空笼[(25 454±12 106)mm 比(16 618±7 542)mm,t=2.295,P=0.030];野生型小鼠在陌生小鼠 箱中的运动距离及运动时间均显著长于空笼[(21 358±5 278)mm比(14 800±4 726)mm、(190.4±70.36) s比 (102.0±32.64)s;t值分别为 2.267、2.573,均P< 0.05]。(3)糖水偏好实验:结果显示,IL-15Rα 基因敲除 小鼠未表现出明显的快感缺失,与野生型小鼠糖水偏好率[(87.97±5.18)%]比较,纯合子和杂合子小鼠糖 水偏好率[分别为(80.02±16.59)%、(84.84±6.53)%]差异均无统计学意义(均P>0.05)。结论 IL-15Rα 敲除小鼠表现出明显的类精神疾病行为,包括筑巢及社交功能障碍,但未表现出抑郁相关快感缺失行为。
基金项目:国家自然科学基金项目(31970918);北京市属医院科研培育计划(PX2018065)
Analysis of psychiatric disorders like behaviors in interleukin-15 receptor α knockout mice
He Yi, Yang Jian, Jia Lina, Ma Chao, Liu Xinyao, Sun Zuoli
()
Abstract:
Objective To study the effect of interleukin-15 receptor α (IL-15Rα) gene knockout on the psychiatric disorders like behavior of mice. Methods 8-week old IL-15Rα knockout mice were divided into homozygous and heterozygous groups, and wild-type mice were used as controls. The genotypes of mice were identified by polymerase chain reaction (PCR). The neuropsychological behaviors were analyzed by nest building test, social interaction test and sucrose preference test. Results The results of PCR showed that the bands of wild-type, homozygote and heterozygote were 171 bp, 280 bp and 171 bp and 280 bp respectively. In this study, 8 wild-type, 14 heterozygotes and 12 homozygotes were included for behavioral testing. (1) Nesting score: Compared with the wild-type, the homozygous knockout mice showed significant nest building dysfunction. The nesting score (1.58±0.79) of homozygous knockout mice was significantly lower than that of wild-type mice (2.71±0.95, P<0.05). At the same time, the nesting score of heterozygous mice (2.21±1.05) was between that of wild-type and homozygous group. Compared with the wild-type and homozygous group, there was no statistical significance (P> 0.05). (2) Three-chamber social test: The data showed that there was no significant difference in the walking distance and walking time of the homozygous knockout mice in the strange mice chamber compared with the empty chamber [Walking distance (22 395±8 664) mm vs (18 057±3 438) mm; Time (178.5±49.05) s vs (161.1±49.84) s; t=1.612, 0.865 respectively; P> 0.05]. The walking distance of the heterozygous group in the strange mice chamber was significantly longer than that in the empty chamber [(25 454±12 106) mm vs (16 618±7 542) mm; t=2.295; P=0.030]. The walking distance and walking time of the wild-type mice in the strange mice chamber was significantly higher than those in the empty chamber [(21 358±5 278) mm vs (14 800±4 726) mm, (190.4±70.36) s vs (102.0±32.64) s; t=2.267, 2.573 respectively; P < 0.05]. (3) Sucrose preference test: IL-15Rα knockout mice showed no obvious anorexia. Compared with the sucrose preference ratio of wild-type mice, there was no statistical significance in that of homozygous (80.02±16.59) % and heterozygous (84.84±6.53) % mice (P > 0.05). Conclusions IL-15Rα knockout mice showed obvious psychiatric disorders like behaviors, including nesting and social dysfunction, but did not show depressiverelated pleasure loss behavior.

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