Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9886570 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2005 | 12 Pages |
Abstract
An elevated plasma level of apolipoprotein B-containing lipoproteins is a risk factor for atherosclerotic cardiovascular disease. Subtle genetic abnormalities in gene expression including an increased expression of the APOB gene may play an important role in determining overall risk. In an attempt to increase mouse Apob expression, we used gene targeting and duplicated â65 kb of genomic DNA containing the Apob locus in its natural genomic position in mice. While we successfully generated mice carrying the Apob gene duplication, the amount of the total Apob mRNA was not increased in their liver. In the intestine, total Apob mRNA was reduced to half of the wild-type mice. Plasma lipids in the Apob duplication mice were not altered. Expression analyses showed that the proximal Apob gene in the duplicated locus was preferentially expressed in both tissues suggesting a limitation of tissue-specific enhancer function. The previously characterized distant intestinal control element was not duplicated, explaining the unequal ratio of intestinal Apob expression. While the existence of an additional liver-specific enhancer element is unknown, our findings suggest the presence of an additional enhancer outside the duplicated region, and that Apob gene expression is more complicated than previously thought.
Keywords
apoBApolipoprotein AIHNF-1CAAT enhancer binding proteinICRARP-1NEOApoAIACEGAPDHPGKapoCIIIDTTNFYHDLLCRVLDLmRNAFPLCTGF-βCREHFHApolipoprotein CIIIC/EBPHnfGATAApolipoprotein BEDTAEthylenediaminetetraacetic acidtransforming growth factor-βbase pairsKilo base pairsdithiothreitolmessenger ribonucleic acidfast protein liquid chromatographyEmbryonic stem cellshepatocyte nuclear factorhepatocyte nuclear factor 1phosphoglycerate kinasehigh density lipoproteinvery low density lipoproteinGene duplicationlocus control regionwild typepolymerase chain reactionPCRThymidine kinase geneNeomycin resistance geneNeo geneCre recombinaseglyceraldehyde 3-phosphate dehydrogenase
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Myron E. Hinsdale, Nobuyo Maeda,