Leukocyte integrin CD11b promoter directs expression in lymphocytes and granulocytes in transgenic mice.
The human leukocyte integrin subunit CD11b is expressed predominantly on myelomonocytic cells. To identify CD11b promoter sequences important for myelomonocytic gene expression and to assess the utility of the CD11b promoter for expressing heterologous genes in vivo, we generated transgenic mice with a human CD4 reporter gene driven by CD11b promoter constructs composed of 1.5, 0.3, or 0.1 kb of DNA sequence 5' to the transcription start site. Using flow cytometry to detect the human CD4 reporter on murine leukocytes, two of three 1.5-kb CD11b promoter founder lines showed surface expression of the human CD4 transgene in granulocytes and lymphocytes. The transgene expression observed in lymphocytes was inappropriate relative to the normal pattern of CD11b expression. Of the eight 0.3-kb or 0.1-kb founder lines, only one 0.1-kb founder line showed transgene expression. The overall pattern of transgene expression among the 11 founder lines does not parallel expression of the endogenous CD11b gene. These studies indicate that additional CD11b regulatory elements will be required to express a reporter gene in vivo in a lineage-specific pattern that mimics the endogenous CD11b gene.
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Medical Research Service, Seattle Veterans Affairs Medical Center, WA.
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Hickstein
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D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D018845:CD11 Antigens / Q000235:genetics*; D015704:CD4 Antigens / Q000096:biosynthesis; D017931:DNA Primers; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000276:immunology*; D013006:Growth Hormone / Q000096:biosynthesis; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping
D015703:Antigens, CD; D018845:CD11 Antigens; D015704:CD4 Antigens; D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D013006:Growth Hormone