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PMID: 7777517 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Scavenger receptor A gene regulatory elements target gene expression to macrophages and to foam cells of atherosclerotic lesions.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 12 ·1995-06-06 ·Pages 5391-5

Horvai A, Palinski W, Wu H, Moulton KS, Kalla K, Glass CK

Abstract

Transcription of the macrophage scavenger receptor A gene is markedly upregulated during monocyte to macrophage differentiation. In these studies, we demonstrate that 291 bp of the proximal scavenger receptor promoter, in concert with a 400-bp upstream enhancer element, is sufficient to direct macrophage-specific expression of a human growth hormone reporter in transgenic mice. These regulatory elements, which contain binding sites for PU.1, AP-1, and cooperating ets-domain transcription factors, are also sufficient to mediate regulation of transgene expression during the in vitro differentiation of bone marrow progenitor cells in response to macrophage colony-stimulating factor. Mutation of the PU.1 binding site within the scavenger receptor promoter severely impairs transgene expression, consistent with a crucial role of PU.1 in regulating the expression of the scavenger receptor gene. The ability of the scavenger receptor promoter and enhancer to target gene expression to macrophages in vivo, including foam cells of atherosclerotic lesions, suggests that these regulatory elements will be of general utility in the study of macrophage differentiation and function by permitting specific modifications of macrophage gene expression.

MeSH Terms
Animals Arteriosclerosis/genetics Cell Differentiation Cells, Cultured Foam Cells/metabolism Gene Targeting Humans Macrophages/cytology,metabolism Membrane Proteins Mice Mice, Transgenic Promoter Regions, Genetic Receptors, Immunologic/genetics Receptors, Lipoprotein Receptors, Scavenger Regulatory Sequences, Nucleic Acid Scavenger Receptors, Class B
Chemicals
Membrane Proteins Receptors, Immunologic Receptors, Lipoprotein Receptors, Scavenger Scarb1 protein, mouse Scavenger Receptors, Class B
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Horvai A
Division of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA.
Palinski W
Wu H
Moulton K S
Kalla K
Glass C K
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.12.5391
Published
1995-06-06
Pages
5391-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC41700
Subset
IM
Grants
NIGMS NIH HHS · GM07198 · United States
NHLBI NIH HHS · HL-14197 · United States
NHLBI NIH HHS · K11-HL02563 · United States
External Links
PubMed source DOI: 10.1073/pnas.92.12.5391 PMC Full Text View journal details
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