Hyperlipidemia was induced in PcntSMC–/– and WT mice by injection of a single dose of adeno-associated virus expressing the pathological human D374Y gain-of-function mutant form of proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9DY; 1.1 × 1011 viral particles) at 6 weeks of age, followed by a high-fat diet (HFD) initiated at 7 weeks of age (23, 24). This evidence concerns the gene PCSK9 and hyperlipidemia.