The human leukocyte integrin CD11a promoter directs expression in leukocytes of transgenic mice.
The human CD11a molecule is expressed specifically on lymphocytes, monocyte/macrophages, and neutrophils, in which it mediates important adhesion-related functions. We used 1.7 kb of regulatory sequences upstream from the human CD11a gene transcription start site to drive expression of a modified human CD4 reporter gene in transgenic mice. The transgene was expressed in a tissue-specific fashion on all leukocytes and paralleled endogenous mouse CD11a expression. All five founder mice expressed the transgene, providing evidence for integration site-independent expression. However, expression was not proportional to transgene copy number. These studies indicate that (1) the mutated human CD4 serves as an excellent reporter for analysis of leukocyte-specific promoters; (2) the CD11a regulatory unit used here represents a novel reagent for targeting gene expression to leukocytes; and (3) additional regulatory regions will be required for copy-number-dependent activity of CD11a regulatory sequences.
Ritchie
K A
KA
Medical Research Service, Seattle Veterans Affairs Medical Center, WA 98108, USA.
Aprikian
A
A
Gollahon
K A
KA
Hickstein
D D
DD
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005813:Genes, Synthetic; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*
D015704:CD4 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D011993:Recombinant Fusion Proteins; D013006:Growth Hormone