Nucleic Acids Research, 2000, Vol. 28, No. 24 4919-4929
© 2000 Oxford University Press
The SP1 sites of the human apoCIII enhancer are essential for the expression of the apoCIII gene and contribute to the hepatic and intestinal expression of the apoA-I gene in transgenic mice
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Departments of Medicine and Biochemistry, Boston University School of Medicine, Boston, MA, USA and 1Department of Pathology, MC 6079, University of Chicago, Chicago, IL 60637, USA
We have generated transgenic mice carrying wild-type and mutant forms of the apolipoprotein (apo)A-I/apoCIII gene cluster. Mutations were introduced either in one or in three SP1 binding sites of the apoCIII enhancer. In mice carrying the wild-type transgene, major sites of apoA-I mRNA synthesis were liver and intestine and minor sites were kidney and, to a lesser extent, other tissues. The major site of chloramphenicol acetyl transferase (CAT) activity (used as a reporter for the apoCIII gene) was liver and minor sites intestine and kidney. A mutation in one SP1 binding site reduced the expression of the apoA-I gene to ~23 and 19% in the liver and intestine, respectively, as compared to the control wild-type. The hepatic expression of the CAT gene was not affected whereas the intestinal expression was nearly abolished. Mutations in three SP1 binding sites reduced the hepatic and intestinal expression of the apoA-I and CAT genes to 14 and 4%, respectively, as compared to the wild-type control, and abolished CAT expression in all tissues. The findings suggest that the SP1 sites of the apoCIII enhancer are required for the expression of the apoCIII gene and also contribute significantly to the hepatic and intestinal expression of the apoA-I gene in vivo.
* To whom correspondence should be addressed. Tel: +1 617 638 5085; Fax: +1 617 638 5141; Email: vzannis{at}bu.edu The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
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