Genetics
First human CETP transgenic mice show that active plasma CETP causally reduces HDL cholesterol (J Biol Chem 1991)
Original title: Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice
A human CETP minigene under control of the mouse metallothionein-I promoter was integrated into the mouse genome to create transgenic mice and directly test the effect of increased plasma CETP on lipoprotein levels. The transgene produced active plasma CETP, and zinc induction of transgene expression significantly depressed serum cholesterol through a specific reduction in HDL cholesterol, with no change in VLDL or LDL total cholesterol content. Plasma and lipoprotein free cholesterol to cholesteryl ester ratios decreased across all fractions, suggesting CETP expression stimulated plasma cholesterol esterification. The authors conclude that high plasma CETP activity may be a direct cause of reduced HDL levels in humans.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.