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Mono-allelic gain-of-function mutations in CSF1R in humans are associated with an autosomal-dominant leukodystrophy and bi-allelic loss-of-function mutations with recessive skeletal dysplasia, brain disorders, and developmental anomalies. Most of the phenotypes observed in these human disease states are also observed in mice and rats with loss-of-function mutations in Csf1r or in Csf1 encoding one of its two ligands. Studies in rodent models also highlight the importance of genetic background and likely epistatic interactions between Csf1r and other loci. The impacts of Csf1r mutations on the brain are usually attributed solely to direct impacts on microglial number and function. However, analysis of hypomorphic Csf1r mutants in mice and several other lines of evidence suggest that primary hydrocephalus and loss of the physiological functions of M\u03d5s in the periphery contribute to the development of brain pathology. In this review, we outline the evidence that CSF1R is expressed exclusively in mononuclear phagocytes and explore the mechanisms linking CSF1R mutations to pleiotropic impacts on postnatal growth and development.<\/jats:p>","DOI":"10.1002\/jlb.mr0519-143r","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T13:34:11Z","timestamp":1563802451000},"page":"205-219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":144,"title":["Phenotypic impacts of CSF1R deficiencies in humans and model organisms"],"prefix":"10.1093","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2615-1478","authenticated-orcid":false,"given":"David A.","family":"Hume","sequence":"first","affiliation":[{"name":"Mater Research Institute, University of Queensland , Woolloongabba, Queensland, 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