Eugene Chen, MD, PhD

Transgenic Rabbits for Cardiovascular Research and Drug Development

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Genome-wide association studies are powerful epidemiological tools to find genes and variants associated with CVD while follow-up biological studies allow us to better understand the etiology and mechanisms of disease and assign causality. The rabbit has a unique value for CVD research, having made considerable contributions to the field. A seminal example is the use of the Watanabe heritable hyperlipidemic (WHHL) rabbits, a model of familial hypercholesterolemia, to confirm the efficacy of statin drugs in lowering plasma lipids and reducing atherosclerosis. The statin drugs were ineffective in mice and rats, likely reflecting that mice have differences in lipid profiles and metabolic pathways compared with human, while rabbits provided a more suitable preclinical model. To overcome a major impediment in CV research and drug development, we have built a leading research team with multiple approaches and expertise to produce gene-targeted (knockout) and transgenic rabbits as CVD model animals for translational research.

---

Frederick Huetwell Professor of Cardiovascular Medicine Director, Center for Advanced Models for Translational Sciences and Therapeutics University of Michigan Ann Arbor, MI