Targeting of transgene expression to monocyte/macrophages by the gp91-phox promoter and consequent histiocytic malignancies.
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.
Skalnik
D G
DG
Division of Hematology/Oncology, Children's Hospital, Boston, MA 02115.
Dorfman
D M
DM
Perkins
A S
AS
Jenkins
N A
NA
Copeland
N G
NG
Orkin
S H
SH
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
D003573:Cytochrome b Group