Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice.
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.
Agellon
L B
LB
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Walsh
A
A
Hayek
T
T
Moulin
P
P
Jiang
X C
XC
Shelanski
S A
SA
Breslow
J L
JL
Tall
A R
AR
D000818:Animals; D001053:Apolipoproteins / Q000235:genetics; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005796:Genes; D005813:Genes, Synthetic; D006023:Glycoproteins; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012727:Sex Characteristics; D015032:Zinc / Q000494:pharmacology
D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D015032:Zinc