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.