This PCSK9DY mutation in ApoE−/− mice mimics a genetic condition of hypercholesterolemia in patients, and it showed a synergistic effect in combination with ApoE deficiency, resulting in a strong increase in serum low-density lipoprotein, accelerated plaque growth and doubling of lesion size compared to wild-type ApoE−/− mice. Here, APOE is linked to familial hypercholesterolemia.