【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.The transgenic mice were created with the microinjection method. Using PCR and Western blotting methods 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 Transgenic mice with human α-synuclein nuclear localization signal were successfully established. Human α-synuclein was widely expressed in various tissues of mice and showed obvious nuclear localization. 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. Conclusion A human α-synuclein nuclear localization signal transgenic mouse model has been successfully established, human α-syn is widely expressed in various tissues of the mice with evident nuclear localization. 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.