| Abstract: |
The human low affinity receptors for the Fc domain of immunoglobulin G, FcγRIII, are encoded by two genes (IIIA and IIIB) which share >95% sequence identity in both coding and flanking sequences. Despite this extraordinary sequence conservation, IIIA is expressed in natural killer (NK) cells and macrophages and is absent in neutrophils, whereas IIIB is expressed only in neutrophils. To determine the molecular basis for this differential expression, we have generated transgenic mice using the genomic sequences of IIIA and IIIB. IIIA and IIIB transgenic mice show faithful reconstitution of this human pattern of cell type specificity. To determine the cis acting sequence elements that confer this specificity, we constructed chimeric genes in which 5.8 kb of 5' sequences of the IIIB gene has been replaced with a homologous region from the IIIA gene, and conversely, IIIA 5' sequences have been substituted for the analogous region of the IIIB gene. Promoter swap transgenic mice that carry IIIA 5' flanking sequences express FcγRIII in macrophages and NK cells. In contrast, promoter swap transgenic mice that contain IIIB 5' sequences express FcγRIII in neutrophils only. These studies define the elements conferring the cell type-specific expression of the human FcγRIII genes within the 5' flanking sequences and first intron of the human FcγRIIIA and FcγRIIIB genes. |
| Keywords: |
promoter region; nonhuman; flow cytometry; animal cell; mouse; animals; mice; gene expression; intron; introns; mice, inbred c57bl; cell type; transgenic mouse; mice, transgenic; conserved sequence; immunoglobulin g; organ specificity; natural killer cell; killer cells, natural; base sequence; fc receptor; neutrophils; dna flanking region; rats; receptor affinity; mice, inbred cba; sequence homology; macrophage; regulatory sequences, nucleic acid; receptors, ige; restriction mapping; promoter regions (genetics); humans; male; female; priority journal; article
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