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

Rocío Rojo, Anna Raper, Derya D. Ozdemir, Lucas Lefevre, Kathleen Grabert, Evi Wollscheid-Lengeling, Barry Bradford, M. Caruso, Iveta Gazova, Alejandra Sanchez, Zofia M. Lisowski, Joana Alves, Irene Molina-Gonzalez, Hayk Davtyan, Rebecca J. Lodge, James D. Glover, Robert Wallace, David A. D. Munro, Eyal David, Ido AmitVéronique E. Miron, Josef Priller, Stephen J. Jenkins, Giles E. Hardingham, Mathew Blurton-Jones, Neil A. Mabbott, Kim M. Summers, Peter Hohenstein, David A. Hume, Clare Pridans

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 similar 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.

Original languageEnglish
Article number3215
JournalNature Communications
Publication statusPublished - 19 Jul 2019


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