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J. Biol. Chem., Vol. 266, Issue 17, 10796-10801, Jun, 1991
LB Agellon, A Walsh, T Hayek, P Moulin, XC Jiang, SA Shelanski, JL Breslow and AR Tall
The human cholesteryl ester transfer protein (CETP) facilitates the
exchange of neutral lipids among lipoproteins. In order to evaluate the
effects of increased plasma CETP on lipoprotein levels, a human CETP
minigene was placed under the control of the mouse metallothionein-I
promoter and used to develop transgenic mice. Integration of the human CETP
transgene into the mouse genome resulted in the production of active plasma
CETP. Zinc induction of CETP transgene expression caused depression of
serum cholesterol due to a significant reduction of high density
lipoprotein cholesterol. There was no change in total cholesterol content
in very low and low density lipoproteins. However, there was a decrease in
the free cholesterol/cholesteryl ester ratio in plasma and in all
lipoprotein fractions of transgenic mouse plasma, suggesting stimulation of
plasma cholesterol esterification. The results suggest that high levels of
plasma CETP activity may be a cause of reduced high density lipoproteins in
humans.
Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
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