The Apolipoprotein E2 (APOE2) knock-in (APOE2ki) mouse model was generated when the murine Apoe gene was replaced by a human Apolipoprotein E2 (APOE*2) gene allele via targeted gene replacement in embryonic stem cells and was first used as a model for hyperlipoproteinemia and atherosclerosis [74]. The gene discussed is APOE; the disease is hyperlipoproteinemia.