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On a C57BL\/6J background homozygous kinase-dead Csf1r mutation (Csf1rE631K\/E631K\u2013E631Km\/m) causes perinatal lethality. By contrast, E631Km\/m mice on a mixed genetic background (C57 \u00d7 BALB\/c) were osteoclast-deficient\/osteopetrotic and growth retarded but did not develop hydrocephalus or other major structural brain abnormalities seen in inbred Csf1r\u2212\/\u2212 mice, and they were viable as adults. Outbred E631Km\/m mice lacked tissue-resident macrophages detected with a Csf1r-EGFP transgene or F4\/80 in most major organs, including the brain, but aside from reproductive organs, which were underdeveloped, no gross histological abnormalities were observed. E631Km\/m genotype was associated with reduced blood monocytes, the loss of circulating C1Q, reduced IGF1, and increased CSF1. In mice, F4\/80+\/CD169+ resident marrow macrophages are believed to be essential components of erythroblastic and hematopoietic island niches. These cells were undetectable in E631Km\/m marrow. Their absence was associated with granulocytosis and B-cell deficiency in marrow, blood, and spleen, whereas the relative abundance of pluripotent and committed progenitors was not affected. Erythropoietic homeostasis was also maintained; erythroblasts were physically associated with a minor residual population of CSF1R-independent CD169\u2212\/F4\/80+ marrow macrophages. We conclude that many developmental and homeostatic functions attributed to mouse resident-tissue macrophages are redundant, species-specific, or restricted to inbred strains.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag074","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T11:33:21Z","timestamp":1781004801000},"source":"Crossref","is-referenced-by-count":4,"title":["Homozygous kinase-dead\n                    <i>Csf1r<\/i>\n                    mutation in outbred mice reveals essential and redundant functions of tissue resident macrophages"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-3641","authenticated-orcid":false,"given":"Sebastien","family":"Jacquelin","sequence":"first","affiliation":[{"name":"Mater Research Institute-The University of Queensland , Translational Research Institute, 37 Kent St, Woolloongabba, Queensland 4102 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