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Rojo, R.; Raper, A.; Ozdemir, D.D.; Lefevre, L.; Grabert, K.; Wollscheid-Lengeling, E.; ... ; Pridans, C. (2019)

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

Article / Letter to editor
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(Delta FIRE/Delta FIRE) 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(Delta FIRE/Delta FIRE) mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r(-/-) rodents. Csf1r(Delta FIRE/Delta FIRE) mice thus...Show moreThe 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(Delta FIRE/Delta FIRE) 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(Delta FIRE/Delta FIRE) mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r(-/-) rodents. Csf1r(Delta FIRE/Delta FIRE) mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals.Show less
All authors
Rojo, R.; Raper, A.; Ozdemir, D.D.; Lefevre, L.; Grabert, K.; Wollscheid-Lengeling, E.; Bradford, B.; Caruso, M.; Gazova, I.; Sanchez, A.; Lisowski, Z.M.; Alves, J.; Molina-Gonzalez, I.; Davtyan, H.; Lodge, R.J.; Glover, J.D.; Wallace, R.; Munro, D.A.D.; David, E.; Amit, I.; Miron, V.E.; Priller, J.; Jenkins, S.J.; Hardingham, G.E.; Blurton-Jones, M.; Mabbott, N.A.; Summers, K.M.; Hohenstein, P.; Hume, D.A.; Pridans, C.
Date
2019-07-19
Journal
Nature Communications
Volume
10
DOI
doi:10.1038/s41467-019-11053-8