Article (Scientific journals)
Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations
Rojo, Rocio; Raper, Anna; Ozdemir, Derya et al.
2019In Nature Communications, 10 (3215)
Peer reviewed
 

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Abstract :
[en] 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Rojo, Rocio
Raper, Anna
Ozdemir, Derya
Lefevre, Lucas
Grabert, Kathleen
Wollscheid-Lengeling, Evi ;  The Roslin Institute and The Royal (Dick) School of Veterinary Studies, University of Edinburgh
Bradford, Barry
Caruso, Melanie
Gazova, Iveta
Sanchez, Alejandra
Lisowski, Zofia
Alves, Joana
Molina-Gonzalez, irene
Davtyan, Hayk
Lodge, Rebecca
Glover, James
Wallace, Robert
Munro, David
David, Eyal
Amit, Ido
Miron, Veronique
Priller, Josef
Jenkins, Stephen
Hardingham, Giles
Blurton-Jones, Mathew
Mabbott, Neil
Summers, Kim
Hohenstein, Peter
Hume, David
Pridans, Clare
More authors (20 more) Less
External co-authors :
yes
Language :
English
Title :
Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations
Publication date :
19 July 2019
Journal title :
Nature Communications
Volume :
10
Issue :
3215
Peer reviewed :
Peer reviewed
Available on ORBilu :
since 23 February 2022

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