Taken together, these data confirm previous reports that injection of mPCSK9-AAV in mice results in overproduction of the gain-of-function mPCSK9, which binds the Ldlr in the liver, resulting in its degradation and a corresponding increase in serum cholesterol levels that eventually leads to hypercholesterolemia when combined with HFD (30, 31). This evidence concerns the gene LDLR and familial hypercholesterolemia.