Hypercholesterolemia was induced in Dennd5b−/− mice by infection with an adeno-associated virus expressing the proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) gain-of-function mutation (PCSK9D377Y) and feeding a Western diet for 12 weeks. This evidence concerns the gene PCSK9 and familial hypercholesterolemia.