The murine macrophage apoB-48 receptor gene ( Apob-48r ): homology to the human receptor 1

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 macro- phage apob-48r cDNA gene sequence and its chromasomal location. The cDNA (3,615 bp) -deduced amino acid (aa) se- quence (942 aa) is � 45% identical to the human macro- phage 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 hydro- phobic 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 ac- tive dimeric ligand binding species (mouse, � 190 kDa; hu- man, � 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 tri- glyceride-rich lipoprotein ligands of the apoB-48R and, of note, uptake of the cholesteryl ester-rich apoB-48-contain- ing very low density lipoproteins that accumulate in athero- sclerosis-prone apoE-deficient mice. Uptake of these ligands by murine apoB-48R-transfected CHOs causes satu- rable, visible cellular triglyceride and cholesterol accumula- tion in vitro that resemble foam cells of atherosclerotic le- sions. In aggregate, the data presented here and that previously published suggest that the apoE-independent murine apoB-48R pathway may contribute to the spontane- ous development of atherosclerotic lesions rich in macro- phage-derived foam cells observed in apoE-deficient mice, a murine model of human atherosclerosis. —Brown, M. L.,