p150glued功能缺失引起小鼠骨骼肌去神经支配  

Loss-of-function of p150glued causes denervation of skeletal muscle in mice

作　　者：宋彬彬 王玉波 杨璇 于佳 Song Binbin;Wang Yubo;Yang Xuan;Yu Jia(Institute of Geriatrics and Rehabilitation,the Beijing Geriatric Hospital,Beijing University of Chinese Medicine,Beijing 100095,China)

机构地区：[1]北京中医药大学附属北京老年医院老年病临床与康复研究所

出　　处：《脑与神经疾病杂志》2019年第12期736-739,共4页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金资助项目（81601117）;北京市自然科学基金资助项目（7184221）;北京市百千万人才工程资助项目（2017A14）;北京市科技新星计划资助项目（Z181100006218045）;北京市医管局临床医学发展专项（ZYLX201833）

摘　　要：目的探讨家族性运动神经元病致病基因DCTN1编码的p150glued蛋白功能缺失对于小鼠脊髓运动神经元对骨骼肌神经支配的影响。方法免疫荧光和激光共聚焦显微镜技术检测对照小鼠(Dctn1^LoxP/LoxP)和p150glued功能缺失小鼠(Dctn1^LoxP/LoxP;Thy1-Cre)的运动神经元轴突末梢对腓肠肌的神经支配情况。结果与Dctn1^LoxP/LoxP小鼠相比,Dctn1^LoxP/LoxP;Thy1-Cre小鼠腓肠肌神经肌肉接头处脊髓运动神经元轴突末梢中p150glued缺失,9月龄时可检测到显著的腓肠肌去神经支配(P<0.05)。结论p150glued功能缺失在导致小鼠脊髓运动神经元变性死亡之前即引起小鼠脊髓运动神经元轴突末梢变性和小鼠骨骼肌去神经支配。Objective To investigate the effects of loss-of-function of p150 glued encoded by motor neuron disease(MND)related DCTN1 gene on the innervation of skeletal muscles by spinal motor neurons in mice.Methods p150 glued expression and synaptic integrity of neuromuscular junction(NMJ)in gastrocnemius of control mice(Dctn1Lox P/Lox P)and p150 glued loss-of-function mice(Dctn1Lox P/Lox P;Thy1-Cre)were examined by immunofluorescence and laser confocal scanning microscopy.Results Compared to Dctn1LoxP/LoxP mice,Dctn1LoxP/LoxP;Thy1-Cre mice showed no p150 glued expression at NMJ of gastrocnemius.And the neuromuscular junctions of gastrocnemius muscles were severely denervated in 9-month-old Dctn1LoxP/LoxP;Thy1-Cre mice(P<0.05).Conclusions Loss-offunction of p150 glued causes early-onset axonal degeneration of spinal motor neurons and denervation of skeletal muscles in mice.

关 键 词：p150glued 去神经支配 神经肌肉接头 运动神经元 轴突 

分 类 号：R744.8[医药卫生—神经病学与精神病学]