Abstract 60: Targeted Disruption of LDLR Causes Hypercholesterolemia and Atherosclerosis in Yucatan Miniature Pigs
Recent progress in engineering the genomes of large animals has spurred increased interest in developing better animal models for diseases where current options are inadequate. Here, we report the creation of Yucatan miniature pigs with targeted disruptions of the low-density lipoprotein receptor (LDLR) gene in an effort to provide an improved model of hypercholesterolemia and atherosclerosis. Yucatan miniature pigs are well established as translational research models because of similarities to humans in physiology, anatomy, genetics, and importantly, size. Using gene targeting and somatic cell nuclear transfer, male and female LDLR+/- pigs were generated. Subsequent breeding of heterozygotes produced LDLR-/- pigs. When fed a standard swine diet, LDLR+/- pigs exhibited a moderate, but consistent increase in total and LDL cholesterol, while LDLR-/- pigs had dramatically elevated levels. Furthermore, this severe hypercholesterolemia in the LDLR-/- pigs resulted in atherosclerotic lesions in the coronary arteries and abdominal aorta that resemble human atherosclerosis. LDLR-targeted Yucatan miniature pigs offer several advantages over existing models including size, consistency, availability, and cost. This new model of cardiovascular disease could be a transformative resource for developing and testing novel detection and treatment strategies for coronary and aortic atherosclerosis and its complications.
- © 2013 by American Heart Association, Inc.