Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis

Abstract

Most of the biological understanding of mechanisms underlying coronary artery disease (CAD) derives from studies of mouse models. The identification of multiple CAD loci and strong candidate genes in large human genome-wide association studies (GWASs) presented an opportunity to examine the relevance of mouse models for the human disease. We comprehensively reviewed the mouse literature, including 827 literature-derived genes, and compared it to human data. First, we observed striking concordance of risk factors for atherosclerosis in mice and humans. Second, there was highly significant overlap of mouse genes with human genes identified by GWASs. In particular, of the 46 genes with strong association signals in CAD GWASs that were studied in mouse models, all but one exhibited consistent effects on atherosclerosis-related phenotypes. Third, we compared 178 CAD-associated pathways derived from human GWASs with 263 from mouse studies and observed that the majority were consistent between the species.

Keywords: CAD risk factors; common and complex disease; diabetes; engineered mouse models; genome-wide association studies; lesions analysis; lipoprotein metabolism; mouse atherosclerosis genes; passenger genes; pathway modeling.