Atherosclerosis Induced by Adeno-Associated Virus Encoding Gain-of-Function PCSK9

Abstract

Induction of atherosclerosis in mice with one or more genetic alterations (e.g., conditional deletion of a gene of interest) has traditionally required crossbreeding with Apoe or Ldlr deficient mice to achieve sufficient hypercholesterolemia. However, this procedure is time consuming and generates a surplus of mice with genotypes that are irrelevant for experiments. Several alternative methods exist that obviate the need to work in mice with germline-encoded hypercholesterolemia. In this chapter, we detail an efficient and increasingly used method to induce hypercholesterolemia in mice through adeno-associated virus-mediated transfer of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene.

Keywords: Adeno-associated virus; Animal models; Atherosclerosis; Hypercholesterolemia; Non-germline; PCSK9; Viral gene transfer.