Human cholesteryl ester transfer protein gene proximal promoter contains dietary cholesterol positive responsive elements and mediates expression in small intestine and periphery while predominant liver and spleen expression is controlled by 5'-distal sequences. Cis-acting sequences mapped in transgenic mice.
Abstract
The plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of high density lipoprotein cholesteryl esters to other lipoproteins and appears to be a key regulated component of reverse cholesterol transport. Earlier studies showed that a CETP transgene containing natural flanking sequences (-3.4 kilobase pairs (kbp) upstream, +2.2 kbp downstream) was expressed in an authentic tissue distribution and induced in liver and other tissues in response to dietary or endogenous hypercholesterolemia. In order to localize the DNA elements responsible for these effects, we prepared transgenic mice expressing six new DNA constructs containing different amounts of natural flanking sequence of the CETP gene. Tissue-specific expression and dietary cholesterol response of CETP mRNA were determined. The native pattern of predominant expression in liver and spleen with cholesterol induction was shown by a -3.4 (5'), +0.2 (3') kbp transgene, indicating no major contribution of distal 3'-sequences. Serial 5'-deletions showed that a -570 base pairs (bp) transgene gave predominant expression in small intestine with cholesterol induction of CETP mRNA in that organ, and a -370 bp transgene gave highest expression in adrenal gland with...Continue Reading
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Citations
Cholesteryl ester transfer protein expression is down-regulated in hyperinsulinemic transgenic mice.
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