title: Complex control of mouse apolipoprotein B gene expression revealed by targeted duplication.
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 approximately 65 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA. Myron-Hinsdale@omrf.ouhsc.edu
authors.forename: Myron E
authors.initials: ME
authors.lastname: Hinsdale
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D005786:Gene Expression Regulation; D018390:Gene Targeting; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001055:Apolipoproteins B; D004041:Dietary Fats; D008055:Lipids