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Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations.
- Source :
-
Nature communications [Nat Commun] 2019 Jul 19; Vol. 10 (1), pp. 3215. Date of Electronic Publication: 2019 Jul 19. - Publication Year :
- 2019
-
Abstract
- The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms-intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1r <superscript>ΔFIRE/ΔFIRE</superscript> mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1r <superscript>ΔFIRE/ΔFIRE</superscript> mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r <superscript>-/-</superscript> rodents. Csf1r <superscript>ΔFIRE/ΔFIRE</superscript> mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals.
- Subjects :
- Animals
Base Sequence
Cell Differentiation
Cell Proliferation
Disease Models, Animal
Embryonic Stem Cells pathology
Epidermal Growth Factor
Female
Gene Expression Regulation
Macrophage Colony-Stimulating Factor genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microglia metabolism
Monocytes metabolism
Phagocytosis
RAW 264.7 Cells
Regulatory Sequences, Nucleic Acid genetics
Genes, fms genetics
Macrophages metabolism
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor genetics
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor metabolism
Sequence Deletion
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31324781
- Full Text :
- https://doi.org/10.1038/s41467-019-11053-8