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Structure, organization, and chromosomal mapping of the gene encoding macrosialin, a macrophage-restricted protein
1Department of Medicine, University of California, Los Angeles 90024, USA.
Abstract:
Murine macrosialin and its human homologue CD68 are heavily glycosylated transmembrane proteins expressed specifically in macrophages and macrophage-related cells. Macrosialin is predominantly a late endosomal protein but is also found on the cell surface where it binds oxidized LDL, an important factor in atherogenesis. We have cloned and sequenced the murine macrosialin gene (Cd68) and localized it by linkage analysis to chromosome 11. The gene is 1908 nucleotides long from the start site of transcription to the end of the 3'UTR. It has six exons, which range in size from 79 to 434 nucleotides. The promoter lacks a classical TATA box but contains other protein binding sites consistent with preferential monocyte/macrophage gene expression. Although the function of macrosialin is unknown, it might play a role in lipoprotein regulation given its binding of oxidized LDL in vitro and its colocalization to a region on chromosome 11 involved in the control of HDL levels.
Insights
Murine macrosialin (Cd68), a macrophage protein binding oxidized LDL, was sequenced. Its gene localization to chromosome 11 suggests a role in lipoprotein regulation and atherogenesis.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Murine macrosialin and human CD68 are heavily glycosylated transmembrane proteins found on macrophages.
- Macrosialin localizes to late endosomes and the cell surface, binding oxidized low-density lipoprotein (LDL), a key factor in atherogenesis.
Purpose of the Study:
- To clone and sequence the murine macrosialin (Cd68) gene.
- To determine the gene's chromosomal localization and analyze its promoter region.
- To investigate the potential role of macrosialin in lipoprotein regulation.
Main Methods:
- Gene cloning and sequencing of murine macrosialin (Cd68).
- Linkage analysis for chromosomal localization.
- Bioinformatic analysis of the gene's promoter region.
Main Results:
- The murine macrosialin (Cd68) gene was cloned and sequenced; it spans 1908 nucleotides with six exons.
- The gene was localized to chromosome 11.
- The promoter lacks a TATA box but contains monocyte/macrophage-specific regulatory elements.
- Macrosialin binds oxidized LDL in vitro and its gene is on chromosome 11, a region linked to HDL control.
Conclusions:
- The murine macrosialin (Cd68) gene structure and regulatory elements support its expression in macrophages.
- Macrosialin's interaction with oxidized LDL and its chromosomal location suggest a role in lipoprotein metabolism and potentially atherogenesis.