Targeting of transgene expression to monocyte/macrophages by the gp91-phox promoter and consequent histiocytic malignancies

David G. Skalnik, David M. Dorfman, Archibald S. Perkins, Nancy A. Jenkins, Neal G. Copeland, Stuart H. Orkin

Research output: Contribution to journalArticle

55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8505-8509
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number19
DOIs
StatePublished - Oct 1 1991

Keywords

  • Cis-regulatory elements
  • Myeloid differentiation
  • Neutrophil cytochrome b

ASJC Scopus subject areas

  • General
  • Genetics

Fingerprint Dive into the research topics of 'Targeting of transgene expression to monocyte/macrophages by the gp91-phox promoter and consequent histiocytic malignancies'. Together they form a unique fingerprint.

Cite this