These results indicate that the CRISPR/Cas9 system-directed by multiple sgRNAs-can induce large fragment deletions of the LDLR gene in rabbits and that these LDLR KO and LDLR/apoE double-KO rabbits should provide novel models for elucidating the mechanisms and therapeutic interventions for hyperlipidemia and atherosclerosis. Here, APOE is linked to atherosclerosis.