Format

Send to

Choose Destination
Nat Commun. 2019 Jul 19;10(1):3215. doi: 10.1038/s41467-019-11053-8.

Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations.

Author information

1
The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
2
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Av. Ignacio Morones Prieto 3000 Pte, Col. Los Doctores, C.P. 64710, Monterrey, N.L., Mexico.
3
Department of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Box 210, SE-171 77, Stockholm, Sweden.
4
The MRC University of Edinburgh Centre for Reproductive Health, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
5
Department of Neurobiology and Behavior, University of California Irvine, 3014 Gross Hall 845 Health Sciences Rd, Irvine, CA, 92697-1705, USA.
6
University of Edinburgh Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
7
The Department of Orthopedic Surgery, University of Edinburgh, Chancellor's Building, Edinburgh BioQuarter, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
8
UK Dementia Research Institute, The University of Edinburgh, Chancellor's Building, Edinburgh BioQuarter, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
9
Department of Immunology, Weizmann Institute of Science, 234 Herzl St., Rehovot, 7610001, Israel.
10
Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, 15 George Square, Edinburgh, EH8 9XD, UK.
11
Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, QLD, 4102, Australia.
12
Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
13
Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, QLD, 4102, Australia. David.Hume@uq.edu.au.
14
University of Edinburgh Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. clare.pridans@ed.ac.uk.
15
Simons Initiative for the Developing Brain, Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK. clare.pridans@ed.ac.uk.

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. Csf1rΔFIRE/ΔFIRE 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, Csf1rΔFIRE/ΔFIRE mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r-/- rodents. Csf1rΔFIRE/ΔFIRE mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center