RGD Reference Report - Analysis of homozygous and heterozygous Csf1r knockout in the rat as a model for understanding microglial function in brain development and the impacts of human CSF1R mutations. - Rat Genome Database

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Analysis of homozygous and heterozygous Csf1r knockout in the rat as a model for understanding microglial function in brain development and the impacts of human CSF1R mutations.

Authors: Patkar, Omkar L  Caruso, Melanie  Teakle, Ngari  Keshvari, Sahar  Bush, Stephen J  Pridans, Clare  Belmer, Arnauld  Summers, Kim M  Irvine, Katharine M  Hume, David A 
Citation: Patkar OL, etal., Neurobiol Dis. 2021 Apr;151:105268. doi: 10.1016/j.nbd.2021.105268. Epub 2021 Jan 12.
RGD ID: 126781687
Pubmed: PMID:33450391   (View Abstract at PubMed)
PMCID: PMC7941205   (View Article at PubMed Central)
DOI: DOI:10.1016/j.nbd.2021.105268   (Journal Full-text)

Mutations in the human CSF1R gene have been associated with dominant and recessive forms of neurodegenerative disease. Here we describe the impacts of Csf1r mutation in the rat on development of the brain. Diffusion imaging indicated small reductions in major fiber tracts that may be associated in part with ventricular enlargement. RNA-seq profiling revealed a set of 105 microglial markers depleted in all brain regions of the Csf1rko rats. There was no evidence of region or sex-specific expression of microglia-associated transcripts. Other than the microglial signature, Csf1rko had no effect on any neuronal or region-specific transcript cluster. Expression of markers of oligodendrocytes, astrocytes, dopaminergic neurons and Purkinje cells was minimally affected. However, there were defects in dendritic arborization of doublecortin-positive neurogenic precursors and expression of poly-sialylated neural cell adhesion molecule (PS-NCAM) in the dentate gyrus of the hippocampus. Heterozygous Csf1rko rats had no detectable brain phenotype. We conclude that most brain developmental processes occur normally in the absence of microglia and that CSF1R haploinsufficiency is unlikely to cause leukoencephalopathy.



Gene Ontology Annotations    

Biological Process

Phenotype Annotations    
Objects Annotated

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


Additional Information