title: Targeting of transgene expression to monocyte/macrophages by the gp91-phox promoter and consequent histiocytic malignancies.
abstract: A component of a heterodimeric cytochrome b, designated gp91-phox, is required for the microbicidal activity of phagocytic cells and is expressed exclusively in differentiated myelomonocytic cells (granulocytes; monocyte/macrophages). In an attempt to identify cis-elements responsible for this restricted pattern of expression, we produced transgenic mice carrying reporter genes linked to the human gp91-phox promoter. Immunohistochemical and RNA analyses indicate that 450 base pairs of the proximal gp91-phox promoter is sufficient to target reporter expression to a subset of monocyte/macrophages. Mice expressing simian virus 40 large tumor antigen under control of the gp91-phox promoter develop monocyte/macrophage-derived malignancies with complete penetrance at 6-12 mo of age and provide an animal model of true histiocytic lymphoma. As these transgenes are inactive in most phagocytic cells that express the endogenous gp91-phox-encoding gene, we infer that additional genomic regulatory elements are necessary for appropriate targeting to the full complement of phagocytes in vivo.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital, Boston, MA 02115.
authors.forename: D G
authors.initials: DG
authors.lastname: Skalnik
authors.forename: D M
authors.initials: DM
authors.lastname: Dorfman
authors.forename: A S
authors.initials: AS
authors.lastname: Perkins
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.forename: S H
authors.initials: SH
authors.lastname: Orkin
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003573:Cytochrome b Group / Q000235:genetics*; D005786:Gene Expression Regulation; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000502:physiology*; D011401:Promoter Regions, Genetic; D013539:Simian virus 40 / Q000235:genetics
chemical_list: D003573:Cytochrome b Group