A macrophage colony-stimulating factor receptor–green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse
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The c-fms gene encodes the receptor for macrophage colony-stimulating factor (CSF-1). The gene is expressed selectively in the macrophage and trophoblast cell lineages. Previous studies have indicated that sequences in intron 2 control transcript elongation in tissue-specific and regulated expression of c-fms. In humans, an alternative promoter was implicated in expression of the gene in trophoblasts. We show that in mice, c-fms transcripts in trophoblasts initiate from multiple points within the 2-kilobase (kb) region flanking the first coding exon. A reporter gene construct containing 3.5 kb of 5' flanking sequence and the downstream intron 2 directed expression of enhanced green fluorescent protein (EGFP) to both trophoblasts and macrophages. EGFP was detected in trophoblasts from the earliest stage of implantation examined at embryonic day 7.5. During embryonic development, EGFP highlighted the large numbers of c-fms-positive macrophages, including those that originate from the yolk sac. In adult mice, EGFP location was consistent with known F4/80-positive macrophage populations, including Langerhans cells of the skin, and permitted convenient sorting of isolated tissue macrophages from disaggregated tissue. Expression of EGFP in transgenic mice was dependent on intron 2 as no lines with detectable EGFP expression were obtained where either all of intron 2 or a conserved enhancer element FIRE (the Fms intronic regulatory element) was removed. We have therefore defined the…
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The reduction of Iba1+ microglia/macrophages by JNJ527 is unsurprising because CSF1R is expressed by microglia and its inhibition reduces microglial proliferation.
“As CSF1R is thought to be expressed exclusively by microglia [34, 63, 64] and its inhibition reduces their proliferation, it is unsurprising that Iba1+ microglia/macrophages were also reduced by this treatment.”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [64]
CSF1R is thought to be expressed exclusively by microglia.
“As CSF1R is thought to be expressed exclusively by microglia [34, 63, 64]”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [64]
Cites
Dai, X.-M., Ryan, G. R., Hapel, A. J., Dominguez, M. G., Russell, R. G., Kapp, S., Sylvestre, V., & Stanley, E. R. (2002) · Blood · doi:10.1182/blood.v99.1.111 · Cited by 1,184 · see citing works
Perry, V. H., Hume, D. A., & Gordon, S. (1985) · Neuroscience · doi:10.1016/0306-4522(85)90215-5 · Cited by 902 · see citing works
Self-citationZhang, D. E., Hetherington, C. J., Chen, H. M., & Tenen, D. G. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.1.373 · Cited by 411 · see citing works
Zhang, D.-E., Hetherington, C. J., Chen, H.-M., & Tenen, D. G. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.1.373-381.1994 · Cited by 411 · see citing works
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Pollard, J. W. (2009) · Nature Reviews Immunology · doi:10.1038/nri2528 · Cited by 1,178 · see citing works
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Qian, B., Deng, Y., Im, J. H., Muschel, R. J., Zou, Y., Li, J., Lang, R. A., & Pollard, J. W. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006562 · Cited by 664 · see citing works
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Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., & Pollard, J. W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026317 · Cited by 649 · see citing works
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Rees, A. J. (2010) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2010.03.002 · Cited by 84 · see citing works
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Obst, J., Simon, E., Martin-Estebane, M., Pipi, E., Barkwill, L. M., Gonzalez-Rivera, I., Buchanan, F., Prescott, A. R., Faust, D., Fox, S., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.579000 · Cited by 33 · see citing works
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Zaid, A., Tharmarajah, K., Mostafavi, H., Freitas, J. R., Sheng, K.-C., Foo, S.-S., Chen, W., Vider, J., Liu, X., West, N. P., et al. (2020) · mBio · doi:10.1128/mbio.03353-19 · Cited by 22 · see citing works
Vicente-Rodríguez, M., Mancuso, R., Peris-Yague, A., Simmons, C., NIMA Consortium, Wlazly, D., Dickinson, A., Foster, A., Knight, C., Leckey, C., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02769-y · Cited by 17 · see citing works
“As CSF1R is thought to be expressed exclusively by microglia [34, 63, 64] and its inhibition reduces their proliferation, it is unsurprising that Iba1+ microglia/macrophages were also reduced by this treatment.”
BackgroundLee, G., Lo, A., Short, S. A., Mankelow, T. J., Spring, F., Parsons, S. F., Yazdanbakhsh, K., Mohandas, N., Anstee, D. J., & Chasis, J. A. (2006) · Blood · doi:10.1182/blood-2006-03-006759 · Cited by 15 · see citing works
- Authors
- Sasmono, R. T., Oceandy, D., Pollard, J. W., Tong, W., Pavli, P., Wainwright, B. J., Ostrowski, M. C., Himes, S. R., & Hume, D. A.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Hume, David A.
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-02-01
- Volume
- 101
- Issue
- 3
- Pages
- 1155-1163
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2130755020
- Cited by
- 662
- References
- 4
- Citations by year
- 2026: 24 · 2025: 19 · 2024: 35 · 2023: 25 · 2022: 28 · 2021: 31 · 2020: 33 · 2019: 38 · 2018: 30 · 2017: 31 · 2016: 29 · 2015: 36 · 2014: 50 · 2013: 39 · 2012: 19
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- c-fms, macrophage colony-stimulating factor receptor, transgenic mice, trophoblast, macrophages, reticuloendothelial system, intron 2, alternative promoters, embryo implantation, yolk sac macrophages, Langerhans cells, tissue-specific gene expression, myeloid development
- MeSH terms
- Animals, Base Sequence, Embryo, Mammalian, Female, Introns, Luminescent Proteins, Lymph Nodes, Mice, Transgenic, Molecular Sequence Data, Phagocytes, Placenta, Promoter Regions, Genetic, Tissue Distribution, Trophoblasts, Gene Expression, Receptor, Macrophage Colony-Stimulating Factor, Genes, Reporter, Transgenes, Myeloid Cells, Green Fluorescent Proteins, Mice
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