Abstract: Objective To compare the behavioral and pathological features of SORL1 gene knockout mice with those of normal mice and APP/PSE1 mice to verify the feasibility of using SORL1 knockout mice as a model of sporadic Alzheimer disease. Methods SORL1 gene of fertilized mouse eggs were edited using Crispr/Case9 technique. SORL1-/- mice were screened and identified by detecting the DNA sequence, and Western blotting was used to detect the expression of SORL1. SORL1-/- mice, control mice and APP/PSE1 mice all underwent Morris water maze test to assess their learning and memory abilities with positioning navigation and space exploration experiments. The expression of APP and Aβ in the brain of the mice was detected using immunohistochemistry and Western blotting, respectively. Results DNA sequencing showed CAAT deletion in SORL1 gene in two chromosomes of SORL1-/- mice, and the control mice had intact SORL1 gene without the deletion; Western blotting did not detect the expression of the SORL1 in the brain of SORL1-/- mice. Morris water maze test showed that in positioning navigation experiment, the average avoidance latency was similar between SORL1-/- mice and APP/PSE1 mice (P>0.05) but increased significantly in both mice as compared with the control group (P<0.05); similar results were obtained in the space exploration experiment. Immunohistochemistry and Western blotting revealed significantly increased APP and Aβ expression in the brain tissue of both SORL1-/- mice and APP/PSE1 mice compared with the control mice without significant differences between the two transgenic mice. Conclusion SORL1-/- mice exhibit similar behavioral and pathological changes with APP/ PSE1 mice and can be used as a model of sporadic Alzheimer’s disease.