RGD Reference Report - Pleiotropic Impacts of Macrophage and Microglial Deficiency on Development in Rats with Targeted Mutation of the Csf1r Locus. - Rat Genome Database

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Pleiotropic Impacts of Macrophage and Microglial Deficiency on Development in Rats with Targeted Mutation of the Csf1r Locus.

Authors: Pridans, Clare  Raper, Anna  Davis, Gemma M  Alves, Joana  Sauter, Kristin A  Lefevre, Lucas  Regan, Tim  Meek, Stephen  Sutherland, Linda  Thomson, Alison J  Clohisey, Sara  Bush, Stephen J  Rojo, RocĂ­o  Lisowski, Zofia M  Wallace, Robert  Grabert, Kathleen  Upton, Kyle R  Tsai, Yi Ting  Brown, Deborah  Smith, Lee B  Summers, Kim M  Mabbott, Neil A  Piccardo, Pedro  Cheeseman, Michael T  Burdon, Tom  Hume, David A 
Citation: Pridans C, etal., J Immunol. 2018 Nov 1;201(9):2683-2699. doi: 10.4049/jimmunol.1701783. Epub 2018 Sep 24.
RGD ID: 41404725
Pubmed: PMID:30249809   (View Abstract at PubMed)
PMCID: PMC6196293   (View Article at PubMed Central)
DOI: DOI:10.4049/jimmunol.1701783   (Journal Full-text)

We have produced Csf1r-deficient rats by homologous recombination in embryonic stem cells. Consistent with the role of Csf1r in macrophage differentiation, there was a loss of peripheral blood monocytes, microglia in the brain, epidermal Langerhans cells, splenic marginal zone macrophages, bone-associated macrophages and osteoclasts, and peritoneal macrophages. Macrophages of splenic red pulp, liver, lung, and gut were less affected. The pleiotropic impacts of the loss of macrophages on development of multiple organ systems in rats were distinct from those reported in mice. Csf1r-/- rats survived well into adulthood with postnatal growth retardation, distinct skeletal and bone marrow abnormalities, infertility, and loss of visceral adipose tissue. Gene expression analysis in spleen revealed selective loss of transcripts associated with the marginal zone and, in brain regions, the loss of known and candidate novel microglia-associated transcripts. Despite the complete absence of microglia, there was little overt phenotype in brain, aside from reduced myelination and increased expression of dopamine receptor-associated transcripts in striatum. The results highlight the redundant and nonredundant functions of CSF1R signaling and of macrophages in development, organogenesis, and homeostasis.

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Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of mononuclear cell proliferation  IMP 41404725 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Csf1r  (colony stimulating factor 1 receptor)
Csf1rtm(EGFP)Tset  (colony stimulating factor 1 receptor; target mutant, Tset)

Genes (Mus musculus)
Csf1r  (colony stimulating factor 1 receptor)

Genes (Homo sapiens)
CSF1R  (colony stimulating factor 1 receptor)

Additional Information