In the transgenic mouse, a specific gene can be transduced or deleted to study its function and relation to human diseases. Recently, various lines of transgenic mice that overexpress or lack a specific gene have been established and are available to study the pathophysiology of human diseases, including atherosclerosis, diabetes, and hyperlipidemia. We have established transgenic mouse lines with an integrated rat apolipoprotein (apo) E gene under control of the metallothionein promoter. Overexpression of apoE in the liver reduced plasma cholesterol and triglyceride levels and prevented dietinduced hypercholesterolemia. Another transgenic model with overexpression of apoE under control of the H2 Ld promoter in the arterial wall was established. In this model, the formation of fatty streak lesions was markedly inhibited, suggesting that apoE has antiatherogenic actions. Finally, we discuss gene therapy, which will be an important therapeutic approach to correct genetic abnormalities found in metabolic diseases.

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