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In mice with a germ-line deletion of FIRE (Fireko), CSF1R expression is undetectable in bone marrow progenitors and classical monocytes, but monocytopoiesis and non-classical monocyte maturation are unaffected. The loss of CSF1R is overcome in part by CSF2 in vitro and inflammatory recruitment in vivo. Fireko mice lack microglia and subpopulations of tissue-resident macrophages in peritoneum, kidney, heart, adipose, liver, skeletal muscle, pancreas, pituitary, adrenal and gonads. Heterozygous mutation impacts CSF1-induced proliferation and postnatal expansion of tissue macrophages. Physiological functions of the heart and kidney were not affected by the absence of macrophages. In a model of renal injury, macrophage recruitment and histopathology in wild-type and Fireko mice were indistinguishable, but there was a male-specific increase in serum creatinine and urea in the Fireko mice. Tissue-resident macrophages depleted in Fireko mice, including microglia, were replaced by donor-derived cells following intraperitoneal transfer of wild-type bone marrow at weaning. The Fireko mouse provides a platform to dissect functions of tissue-resident macrophages in development, homeostasis and pathology.<\/jats:p>","DOI":"10.1242\/dev.205655","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T07:28:13Z","timestamp":1782458893000},"source":"Crossref","is-referenced-by-count":2,"title":["Depletion and replacement of tissue-resident macrophages in mice with germ-line deletion of a conserved enhancer in the\n                    <i>Csf1r<\/i>\n                    locus"],"prefix":"10.1242","volume":"153","author":[{"given":"Yajun","family":"Liu","sequence":"first","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-3641","authenticated-orcid":false,"given":"Sebastien","family":"Jacquelin","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isis","family":"Taylor","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma K.","family":"Green","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omkar L.","family":"Patkar","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Keshvari","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginell","family":"Ranpura","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conan J. O.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Jessen","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Allavena","sequence":"additional","affiliation":[{"name":"School of Veterinary Science, The University of Queensland 2 , Gatton, QLD 4343 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Gallerand","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, CNRS 3 , LP2M Nice ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stoyan","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, CNRS 3 , LP2M Nice ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Adamson","sequence":"additional","affiliation":[{"name":"University of Manchester 4 Faculty of Biology, Medicine and Health , , Manchester M13 9PL,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil E.","family":"Humphreys","sequence":"additional","affiliation":[{"name":"University of Manchester 4 Faculty of Biology, Medicine and Health , , Manchester M13 9PL,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim M.","family":"Summers","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine M.","family":"Irvine","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2615-1478","authenticated-orcid":false,"given":"David A.","family":"Hume","sequence":"additional","affiliation":[{"name":"Mater Research Institute-University of Queensland, Translational Research Institute 1 , Woolloongabba, Brisbane, QLD 4102 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"2026071307524836700_DEV205655C1","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1038\/s41590-025-02217-4","article-title":"Genetic variation in the activity of a TREM2-p53 signaling axis determines oxygen-induced lung injury","volume":"26","author":"Abe","year":"2025","journal-title":"Nat. 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