As the leading cause of death in the modern world, cardiovascular disease is a symptomatic end stage of different diseases, thus is multifactorial and polygenetic in character. The two major underlying causes are disorders of lipid metabolism and metabolic syndrome. The ability to develop preventative and ameliorative treatments will depend on widely-accessible animal models that mimic human metabolism and will be large enough to permit physiological and metabolic studies. Extensive studies have been conducted for the role of Apolipoprotein (ApoE), Low-Density Lipoprotein Receptor (Ldlr), and Leptin in cardiovascular disease and lipoprotein transport. The advent of Zinc Finger Nuclease (ZFN) technology has enabled the creation of ApoE, Ldlr and Leptin knockout rat models for studying atherosclerosis, hypertension, and type II diabetes. The Leptin model show elevated triglyceride level and are almost twice the size of wild type litter-mates. In the Ldlr model we see a significant higher cholesterol level comparing to the control. I will discuss the technology used, methodology for creation, and the phenotypic characterization of the above mentioned knockout rat models. SAGE^TM Labs will continue to support the research effort towards finding the necessary cures for the diseases by making transgenic animal models available for the study of cardiovascular, renal and metabolic diseases.