Abstract: Objective The CRISPR/Cas9 system was utilized to generate an Apoe knockout mice model to support further investigations of the role of Apoe in lipid metabolism and atherosclerosis. Methods Two single guide RNAs designed for Apoe in C57BL/6J mice were co-injected with Cas9 mRNA into fertilized eggs, followed by transplantation into ICR recipient mice to obtain F0 generation mice. KO mice were identified by polymerase chain reaction (PCR) screening of tail DNA.