Human leukocyte integrin CD18 promoter directs low levels of expression of a mutated human CD4 reporter gene in leukocytes of transgenic mice.
The human leukocyte integrin CD18 molecule exists on the leukocyte surface in heterodimeric complexes with individual CD11 subunits, which mediate important leukocyte adhesion reactions. The CD18 subunit is developmentally regulated with the highest levels present on mature leukocytes of all lineages. To identify the regulatory sequences responsible for the tissue- and stage-specific expression of the CD18 subunit, we used 3.5 kb of regulatory sequence upstream from the human CD18 gene transcription start site to drive expression of a modified human CD4 reporter gene in transgenic mice. Despite the inclusion of Sp1 and PU.1 sites in the construct, and the generation of founder lines possessing multiple copies of the transgene, the reporter gene was expressed in low levels in the leukocytes of the transgenic mice. These studies indicate that although PU.1 and Sp1 sites are required for CD18 promoter activity in vitro, additional regulatory regions appear to be required for high levels of copy number dependent expression in vivo.
Kwiatkowski
B A
BA
Medical Research Service, Seattle Veterans Affairs Medical Center, Washington 98108, USA.
Embree
L J
LJ
Ritchie
K A
KA
Hickstein
D D
DD
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D018821:CD18 Antigens / Q000235:genetics*; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics; D005434:Flow Cytometry; D015870:Gene Expression; D013006:Growth Hormone / Q000096:biosynthesis; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D013997:Time Factors
D015703:Antigens, CD; D018821:CD18 Antigens; D015704:CD4 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D011994:Recombinant Proteins; D013006:Growth Hormone