The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]

Abstract

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.

Human ALX receptor regulates neutrophil recruitment in transgenic mice: roles in inflammation and host defense

“…This promoter was engineered for targeted expression in myeloid cells (14). Earlier studies by Dziennis et al (14) using founders with two different reporter genes (␤-galactosidase and Thy1.1 surface marker) downstream of this CD11b promoter fragment showed appreciable levels of transgene expression directed to mature myeloid cells. To this end, for the present experiments the transgenic founders were generated by DNA injections of fertilized FvB oocytes.…”

Uptake and presentation of exogenous antigen and presentation of endogenously produced antigen by skin dendritic cells represent equivalent pathways for the priming of cellular immune responses following biolistic DNA immunization

“…In contrast, our results show potent and long-lasting induction of CD8 + CTLs after biolistic transfection employing the fascin promoter. As the activities of the isolated human CD11b promoter and murine Ea promoter have been documented solely in macrophages/ monocytes, 20,[46][47][48][49] and not in Langerhans cells or DCs, it cannot be ruled out that the efficiency of transgene expression following transfection of DCs of the skin has been low in the study of Cho et al 20 Hence, the discrepancy might be explained by the notion that the targeting of transgene expression mainly to macrophages led to suboptimal activation of naïve CD8 + T cells in the lymph nodes. Moreover, because biosynthesis of MHC class II molecules is down-regulated during DC maturation, 50 promoter activity and concomitantly transgene expression were probably also down-regulated in the directly transfected DCs.…”

The use of human CD68 transcriptional regulatory sequences to direct high‐level expression of class A scavenger receptor in macrophages in vitro and in vivo

“…The majority of these promoters, including human CD11b, human lysozyme and human c-fes, are from genes that show myeloid-restricted expression, and so at best the transgene is expressed by both neutrophils and Mws. 23,25,26,28,52 Human SR-A promoter elements direct transgene expression in Mws in mouse atherosclerotic lesions, spleen and testes, but not in other organs that contain signi®cant numbers of Mws. 24 However, it is dif®cult to compare levels of transgene expression between transgenic lines owing to differences in transgene copy number and the reporter gene used.…”