RAC1、RAC3和IQGAP1在SOD1^(G93A)突变小鼠脊髓中的表达  

Expressions of RAC1,RAC3,and IQGAP1 in the spinal cord of SOD1^(G93A) mutant mice

作　　者：王雪枚 齐波 霍姿君 赵建涛 管英俊[1] 陈燕春[1] 刘焕彩[3] 张凌云 Wang Xuemei;Qi Bo;Huo Zijun;Zhao Jiantao;Guan Yingjun;Chen Yanchun;Liu Huancai;Zhang Lingyun(Department of Histology and Embryology and Key Laboratory of Neurological Diseases and Regenerative Repair,Weifang Medical University,Weifang 261053;Weifang Maternal and Child Health Hospital,Weifang 261011;Affiliated Hospital of Weifang Medical University,Weifang 261031)

机构地区：[1]潍坊医学院组织与胚胎学教研室暨神经疾病与再生修复重点实验室,潍坊261053 [2]潍坊市妇幼保健院,潍坊261011 [3]潍坊医学院附属医院,潍坊261031

出　　处：《神经解剖学杂志》2022年第5期499-506,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81871006);山东省自然科学基金(ZR2020MH150);山东省高等学校青创科技支持计划(2019KJK004);山东省高校科技发展计划项目重点项目(J18KZ013)。

摘　　要：目的:检测Ras相关C3肉毒菌毒物底物1(RAC1)、Ras相关C3肉毒菌毒物底物3(RAC3)和IQ结构域GTP酶活化蛋白1(IQGAP1)在SOD1^(G93A)突变小鼠脊髓中的表达变化。方法:选取SOD1^(G93A)突变小鼠与野生型(WT)小鼠作为动物模型,将其分为症状前期(出生70 d)、症状早期(出生95 d)、症状中期(出生108 d)和症状晚期(出生122 d)4个组别,利用RT-PCR检测小鼠脊髓中RAC1、RAC3和IQGAP1 mRNA表达,利用Western Blot和免疫荧光染色检测RAC1、RAC3和IQGAP1蛋白表达与定位。结果:与同窝WT小鼠相比,RAC1 mRNA表达水平在出生不同时间点SOD1^(G93A)突变小鼠脊髓中无明显变化;在出生95、108和122 d RAC3 mRNA均明显降低,IQGAP1 mRNA均明显升高;RAC1、RAC3和IQGAP1蛋白在出生95、108和122 d表达均明显降低;RAC1、RAC3、IQGAP1免疫阳性细胞主要分布在脊髓前角,即运动神经元所在的部位,RAC1、RAC3和IQGAP1均与神经元特异性核抗原(NeuN)标记的神经元共表达。结论:SOD1^(G93A)突变小鼠脊髓中RAC1、RAC3和IQGAP1的表达异常与肌萎缩侧索硬化症(ALS)的发病密切相关。Objective:To detect the expression of Ras-related C3 botulinum toxin substrate 1(RAC1),Ras-related C3 botulinum toxin substrate 3(RAC3)and IQ motif containing GTPase activating protein 1(IQGAP1)in the spinal cord of SOD1^(G93A) mutant mice.Methods:SOD1^(G93A) mutant mice and wild-type(WT)mice were selected as animal models.They were divided into four groups:pre-symptomatic(70 days after birth),early symptoms(95 days after birth),middle symptoms(108 days after birth)and late symptoms(122 days after birth).The mRNA expression of RAC1,RAC3,and IQGAP1 in the spinal cord of mice was detected by RT-PCR.The expression and localization of RAC1,RAC3 and IQGAP1 protein were detected by Western Blot and immunofluorescence staining.Results:Compared with WT littermate,the expression level of RAC1 mRNA in the spinal cord of SOD1^(G93A) mutant mice had no significant change at different time points after birth,and RAC3 mRNA was decreased significantly at 95,108 and 122 days after birth.The level of IQGAP1 mRNA was increased significantly.The expression of RAC1,RAC3 and IQGAP1 protein was decreased significantly in spinal cord tissue of SOD1^(G93A) mutant mice at 95,108 and 122 days after birth.RAC1,RAC3 and IQGAP1 immunopositive cells were mainly distributed in the anterior horn of spinal cord,where the motor neurons were located.RAC1,RAC3,and IQGAP1 were co-expressed with neuron specific nuclear protein(NeuN).Conclusion:The abnormal expression of RAC1,RAC3,and IQGAP1 in the spinal cord of SOD1^(G93A) mutant mice is closely related to the pathogenesis of amyotrophic lateral sclerosis(ALS).

关 键 词：肌萎缩侧索硬化症 脊髓 RAC1 RAC3 IQGAP1 SOD1^(G93A)突变小鼠 

分 类 号：R744.8[医药卫生—神经病学与精神病学]