The invention provides genetically altered fish of the family Cyprinidae, or genus Danio, including zebrafish (Danio rerio) and host cells from these animals, where the fish have been genetically altered to lack or have a modified gene related to lipid metabolism, for example, an ApoE, ApoAI and/or LDL-R gene. In another aspect, the invention is directed to drug design or discovery using the animal or cell models of the invention and/or wild type zebrafish, and by administering an altered diet and/or environment to the animal of invention. The invention also provides methods for screening for a compound capable of ameliorating or preventing or reversing: atherosclerosis hyperlipidemia lipoprotein oxidation the accumulation of lipid in a blood vessel wall vascular inflammation associated with lipid accumulation in a blood vessel wall acute atherosclerosis-associated events heart attack stroke.
