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 d...

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Bibliographic Details
Published in:The Journal of biological chemistry 1991-06, Vol.266 (17), p.10796-10801
Main Authors: AGELLON, L. B, WALSH, A, HAYEK, T, MOULIN, P, XIAN CHENG JIANG, SHELANSKI, S. A, BRESLOW, J. L, TALL, A. R
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Animals
Apolipoproteins - genetics
Biological and medical sciences
Carrier Proteins - blood
Carrier Proteins - genetics
Cholesterol Ester Transfer Proteins
Cholesterol, HDL - blood
Female
Fundamental and applied biological sciences. Psychology
Genes
Genes, Synthetic
Glycoproteins
Humans
Lipids
Male
Mice
Mice, Inbred Strains
Mice, Transgenic
Miscellaneous
Other biological molecules
Sex Characteristics
Zinc - pharmacology
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1016/s0021-9258(18)99088-5