Abstract: Objective To construct and characterize tau and mutant tau protein cell and animal models. Methods Different plasmids were transfected into HEK293 cells,and cell models overexpressing wild-type tau or P301L/P301S mutant tau were constructed. rTg4510 mice (P301L mutant tau transgenic mice) and PS19 mice (P301S mutant tau transgenic mice) were introduced and bred. The expression of total tau and phosphorylated tau protein was detected with Western blotting. The expression of phosphorylated tau protein in the brain of transgenic mice was detected with immunohistochemistry. The morphology of HEK293 cells was observed with immunofluorescence. Results In this study,cell and animal models overexpressing tau were successfully constructed. The tau protein expression in these models were significantly increased,and the phosphorylation levels of tau protein were significantly higher than that of the control group. In the cell and animal models of different mutation types,changes in phosphorylation levels and microtubule morphology at different sites showed slight differences. Conclusion We successfully constructed P301L/P301S mutant tau cell and animal models with significant tau hyperphosphorylation and changes in cell microtubule morphology. These models might provide alternative for proper disease model in the studies of tau and tauopathies,such as Alzheimer's disease.

Key words: microtubule -associated protein tau, transfected cell model, transgenic animal model, microtubule