ABSTRACT
In humans, lipoprotein disorders are strongly associated with coronary heart disease susceptibility. Several types o f abnormal lipoprotein patterns are commonly observed in heart attack victims, including elevated LDL choles terol; reduced HDL cholesterol, usually with increased triglycerides; elevated chylomicron remnant and IDL cholesterol levels; and elevated levels o f Lp(a) particles. These patterns are caused by environmental and genetic factors that alter the synthesis, processing, or catabolism o f lipoprotein particles. Over the last decade, genes have been isolated that code for proteins that directly interact with plasma lipids. There are approximately 17 such lipoprotein transport proteins, including apolipoproteins that coat lipoprotein particles, lipoprotein-processing proteins, and lipoprotein receptors (Table 1). The genes coding for these proteins have all turned out to be single-copy in the human genome. They have been sequenced, mapped, and used as candidate genes to identify mutations underlying lipoprotein phenotypes associated with coronary heart disease susceptibility (1). The lipoprotein transport genes have also been used to make transgenic and knockout animals, principally mice, which have provided new insights into how these genes are expressed and the functions they serve in an intact organism. Either singly or combined through crossbreeding, these genetically altered mice are now being used to make animal models o f human lipoprotein disorders associated with coronary heart disease susceptibility (Table 2) (2-4). In at least one instance, a mouse has been produced that develops diffuse fibroproliferative atherosclerotic lesions very much like those seen in humans.
