中国实验动物学报2024，Vol.32Issue(3)：307-316,10.DOI:10.3969/j.issn.1005-4847.2024.03.004
核定位人源α-突触核蛋白转基因小鼠的建立
Establishment of the human α-synuclein nuclear localization signal transgenic mice
摘要
Abstract
Objective To establish a human α-synuclein nuclear localization signal transgenic mouse model and investigate the effects of α-synuclein nuclear localization on the behavior of mice.Methods Human α-synuclein nuclear localization signal and EGFP lentiviral vectors were constructed.Transgenic mice were created with the microinjection method.Using PCR and Western Blot method to identify the genotypes and protein expression of the transgenic founder mice and their offsprings.The immunofluorescence was used to examine the localization of human α-synuclein in the mouse brain tissue.The behavioral changes of the transgenic mice were evaluated by the open field test,rotarod test,and O maze test.Results The h SNCA-NLS gene was successfully inserted into the mouse genome,the human α-syn was successfully expressed,and the human α-syn has localized with the nuclear.Further studies found that human α-synuclein nuclear localization signal transgenic mice had significant motor dysfunction,astrocyte proliferation and inflammatory response at 2 months of age and exhibited significant anxiety-like symptoms and reduced expression of the γ-aminobutyric acid(GABA)gene at 9 months of age,which persisted until 12 months of age.Conclusions A human α-synuclein nuclear localization signal transgenic mouse model has been successfully established.The mice exhibit significant motor dysfunction and anxiety-like symptoms.The successful establishment of this model provides a foundation for studying the role of α-syn nuclear localization in Parkinson's disease.关键词
人源α-突触核蛋白/小鼠/核定位/转基因/运动功能障碍Key words
human α-synuclein/mouse/nuclear localization/transgenic/motor dysfunction分类
生物科学引用本文复制引用
韦梦晨,范胜涛,吴海婷,张艺薇,王子鸥,黄璋琼..核定位人源α-突触核蛋白转基因小鼠的建立[J].中国实验动物学报,2024,32(3):307-316,10.基金项目
云南省技术创新人才培养对象项目(202105AD160018,202005AD160006),中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-043),国家自然科学基金联合基金项目(U2202214),科技创新2030-重大专项(2023ZD0406306). Funded by Technology Innovation Talents Project of Yunnan Province(202105AD160018,202005AD160006),CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-043),Joint Funds of the National Natural Science Foundation of China(U2202214),Scientific and Technological Innovation 2030(2023ZD0406306). （202105AD160018,202005AD160006）
