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Journal of Lipid Research, Vol. 43, 1181-1191, August 2002
Copyright © 2002 by Lipid Research, Inc.

The murine macrophage apoB-48 receptor gene (Apob-48r)

Matthew L. Brown^*, Katsumasa Yui, Jonathan D. Smith^**, Renée C. LeBoeuf, Wei Weng, Patrick K. Umeda, Ran Li^*, Ruiling Song^*, Sandra H. Gianturco^2,* and William A. Bradley^2,*

^* Department of Medicine, Division of Gerontology and Geriatrics, University of Alabama at Birmingham, Birmingham, AL 35294-0012
Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL 35294-0012
The Third Department of Internal Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
^** Rockefeller University, 1230 York Avenue, Box 179, New York, NY 10021
Department of Pathobiology, University of Washington, Seattle, WA 98195-3410
InGenious Targeting Laboratory, LIHTI Building, Suite 106, Stony Brook, NY 11790-3350

² To whom correspondence should be addressed. e-mail: shg{at}uab.edu or wbradley{at}uab.edu

Previously we cloned the human macrophage apolipoprotein B-48 receptor (ApoB-48R) and documented its expression in human atherosclerotic foam cells (1). Now we have identified and characterized the murine macrophage apob-48r cDNA gene sequence and its chromasomal location. The cDNA (3,615 bp) -deduced amino acid (aa) sequence (942 aa) is 45% identical to the human macrophage APOB-48R, but not to other known gene families. The murine Apob-48r gene, like the human APOB-48R gene, consists of four exons interrupted by three small introns and is syntenically located on chromosome 7. Functionally significant conserved domains include an N-terminal hydrophobic domain, a glycosaminoglycan attachment site, an N-glycosylation site, and an ExxxLL internalization motif C-terminal to the putative internal transmembrane domain. Two conserved coiled-coil domains are likely involved in the spontaneous homodimerization that generates the active dimeric ligand binding species (mouse, 190 kDa; human, 200 kDa). Transfection of the murine apoB-48R into Chinese hamster ovary cells (CHOs) confers apoB-48R function: rapid, high-affinity, specific uptake of known triglyceride-rich lipoprotein ligands of the apoB-48R and, of note, uptake of the cholesteryl ester-rich apoB-48-containing very low density lipoproteins that accumulate in atherosclerosis-prone apoE-deficient mice. Uptake of these ligands by murine apoB-48R-transfected CHOs causes saturable, visible cellular triglyceride and cholesterol accumulation in vitro that resemble foam cells of atherosclerotic lesions.

In aggregate, the data presented here and that previously published suggest that the apoE-independent murine apoB-48R pathway may contribute to the spontaneous development of atherosclerotic lesions rich in macrophage-derived foam cells observed in apoE-deficient mice, a murine model of human atherosclerosis.

Abbreviations: apo, apolipoprotein; apoB-48R, apolipoprotein B-48 receptor; CHO, Chinese hamster ovary cell; GPDH, glyceraldehyde-3-phosphate dehydrogenase; HTG, hypertriglyceridemic; TRL, triglyceride-rich lipoproteins

Supplementary key words atherosclerosis • chylomicrons • hypertriglyceridemia • postprandial lipoproteins

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