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The expression of <jats:italic>Csf2<\/jats:italic>, encoding granulocyte\u2010macrophage CSF (GM\u2010CSF) and of <jats:italic>Csf3<\/jats:italic>, encoding granulocyte CSF (G\u2010CSF), are elevated in both mouse and human CRL brains. While monoallelic targeting of <jats:italic>Csf2<\/jats:italic> has been shown to attenuate many behavioral and histological deficits of <jats:italic>Csf1r<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice, including cognitive dysfunction and demyelination, the contribution of <jats:italic>Csf3<\/jats:italic> has not been explored. In the present study, we investigate the behavioral, electrophysiological and histopathological phenotypes of <jats:italic>Csf1r<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice following monoallelic targeting of <jats:italic>Csf3.<\/jats:italic> We show that <jats:italic>Csf3<\/jats:italic> heterozygosity normalized the <jats:italic>Csf3<\/jats:italic> levels in <jats:italic>Csf1r<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mouse brains and ameliorated anxiety\u2010like behavior, motor coordination and social interaction deficits, but not the cognitive impairment of <jats:italic>Csf1r<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice. <jats:italic>Csf3<\/jats:italic> heterozygosity failed to prevent callosal demyelination. However, consistent with its effects on behavior, <jats:italic>Csf3<\/jats:italic> heterozygosity normalized microglial morphology in the cerebellum and in the ventral, but not in the dorsal hippocampus. <jats:italic>Csf1r<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice exhibited altered firing activity in the deep cerebellar nuclei (DCN) associated with increased engulfment of glutamatergic synapses by DCN microglia and increased deposition of the complement factor C1q on glutamatergic synapses. These phenotypes were significantly ameliorated by monoallelic deletion of <jats:italic>Csf3<\/jats:italic>. Our current and earlier findings indicate that G\u2010CSF and GM\u2010CSF play largely non\u2010overlapping roles in CRL\u2010like disease development in <jats:italic>Csf1r<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice.<\/jats:p>","DOI":"10.1002\/glia.24310","type":"journal-article","created":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T14:30:45Z","timestamp":1669473045000},"page":"775-794","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Elevated granulocyte colony stimulating factor (<scp>CSF<\/scp>) causes cerebellar deficits and anxiety in a model of <scp>CSF<\/scp>\u20101 receptor related leukodystrophy"],"prefix":"10.1002","volume":"71","author":[{"given":"Fabrizio","family":"Biundo","sequence":"first","affiliation":[{"name":"Department of Developmental and Molecular Biology Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Violeta","family":"Chitu","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaafar","family":"Tindi","sequence":"additional","affiliation":[{"name":"The Dominick P. Purpura Department of Neuroscience Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nesha S.","family":"Burghardt","sequence":"additional","affiliation":[{"name":"Department of Psychology Hunter College, The City University of New York  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel G. L.","family":"Shlager","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harmony C.","family":"Ketchum","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"DeTure","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zbignew K.","family":"Wszolek","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamran","family":"Khodakhah","sequence":"additional","affiliation":[{"name":"The Dominick P. 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