In the transgenic mouse, a specific gene can be transduced or deleted
to study its function and relation to human diseases. Recently, variou
s lines of transgenic mice that overexpress or lack a specific gene ha
ve been established and are available to study the pathophysiology of
human diseases, including atherosclerosis, diabetes, and hyperlipidemi
a. We have established transgenic mouse lines with an integrated rat a
polipoprotein (apo) E gene under control of the metallothionein promot
er. Overexpression of apoE in the liver reduced plasma cholesterol and
triglyceride levels and prevented diet-induced 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, sugges
ting that apoE has antiatherogenic actions. Finally, we discuss gene t
herapy, which will be an important therapeutic approach to correct gen
etic abnormalities found in metabolic diseases.