Padi2敲除加重社会隔离下小鼠的抑郁样行为  

Padi2 knockout exacerbates depressive⁃like behaviors in socially isolated mice

作　　者：赵亚 吕冲昊 罗世帆 刘可 郑泽民 白冰 师长宏 ZHAO Ya;LYU Chonghao;LUO Shifan;LIU Ke;ZHENG Zemin;BAI Bing;SHI Changhong(Laboratory Animal Center,Air Force Military Medical University,Xi’an 710032,China;the First Clinical Medical College,Gansu University of Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]空军军医大学实验动物中心,西安710032 [2]甘肃中医药大学第一临床医学院,兰州730000

出　　处：《中国实验动物学报》2025年第2期190-203,共14页Acta Laboratorium Animalis Scientia Sinica

基　　金：陕西省创新能力支持计划(2022PT-36,2022PT-42);军队实验动物专项课题(SYDW2020-20);国家自然青年科学基金(32300428)。

摘　　要：目的 探讨肽基精氨酸脱亚胺酶2(Padi2)敲除对社会隔离下小鼠抑郁样行为的影响。方法利用CRISPR/Cas9技术,建立C57BL/6J背景的Padi2敲除(Padi2^(-/-))小鼠模型,通过基因型鉴定和RT-qPCR检测Padi2的敲除效果;选取6周龄的雄性Padi2^(-/-)小鼠和野生型C57BL/6J小鼠分别设置正常饲养组和社会隔离组,每组15只,正常饲养组5只/笼饲养,社会隔离组1只/笼饲养,每周称重一次,4周后进行强迫游泳以及旷场实验;行为学实验结束后,取各组小鼠脑组织,通过免疫荧光检测小鼠脑内小胶质细胞变化情况。结果成功建立Padi2^(-/-)小鼠,正常饲养组中Padi2^(-/-)小鼠和C57BL/6J小鼠行为学无差异;社会隔离后,与C57BL/6J小鼠相比,Padi2^(-/-)小鼠抑郁症状显著升高,体质量增长明显,脑组织中小胶质细胞数目显著增多。结论 Padi2敲除加重社会隔离下小鼠的抑郁样行为以及肥胖,提示Padi2参与抑郁症进展,可能是抑郁症预防和治疗的有效靶点。Objective To explore the impact of peptidylarginine deiminase 2(Padi2)⁃knockout on depressive⁃like behaviors in socially isolated mice.Methods Using CRISPR/Cas9 technology,a Padi2⁃knockout(Padi2^(-/-))mouse model with a C57BL/6J background was established,and the effect of Padi2 knockout was identified by genotyping and RT⁃qPCR detection.Six⁃week⁃old male Padi2^(-/-)mice and wild⁃type C57BL/6J mice were selected and divided into normal rearing and social isolation groups,with 15 mice per group.The normal rearing group mice were housed with 5 mice per cage,and the social isolation group was housed with 1 mouse per cage,and weighed once a week.After 4 weeks,forced swimming and open field tests were conducted.After the behavioral experiments,brain tissues were taken from mice in each group,and changes in microglia in the brains were detected by immunofluorescence.Results We successfully established Padi2^(-/-)mice.There was no difference in behavior between Padi2^(-/-)mice and C57BL/6J mice in the normal rearing group.After social isolation,compared with C57BL/6J mice,Padi2^(-/-)mice showed a significant increase in depressive symptoms,obvious weight gain,and a significant increase in the number of microglia in brain tissue.Conclusions Padi2 knockout exacerbated depressive⁃like behaviors and obesity in socially isolated mice,indicating that Padi2 is involved in the progression of depression and may be an effective target for the prevention and treatment of depression.

关 键 词：抑郁样行为 肽基精氨酸脱亚胺酶2 社会隔离 基因敲除 小胶质细胞 

分 类 号：Q95-33[生物学—动物学]