Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects
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- 1 January 2002
- journal article
- Published by American Society of Hematology in Blood
- Vol. 99 (1), 111-120
- https://doi.org/10.1182/blood.v99.1.111
Abstract
The effects of colony-stimulating factor 1 (CSF-1), the primary regulator of mononuclear phagocyte production, are thought to be mediated by the CSF-1 receptor (CSF-1R), encoded by the c-fms proto-oncogene. To investigate the in vivo specificity of CSF-1 for the CSF-1R, the mouse Csf1r gene was inactivated. The phenotype ofCsf1−/Csf1r− mice closely resembled the phenotype of CSF-1-nullizygous(Csf1op /Csf1op) mice, including the osteopetrotic, hematopoietic, tissue macrophage, and reproductive phenotypes. Compared with their wild-type littermates, splenic erythroid burst-forming unit and high-proliferative potential colony-forming cell levels in bothCsf1op /Csf1op andCsf1−/Csf1r− mice were significantly elevated, consistent with a negative regulatory role of CSF-1 in erythropoiesis and the maintenance of primitive hematopoietic progenitor cells. The circulating CSF-1 concentration inCsf1r−/Csf1r− mice was elevated 20-fold, in agreement with the previously reported clearance of circulating CSF-1 by CSF-1R–mediated endocytosis and intracellular destruction. Despite their overall similarity, several phenotypic characteristics of theCsf1r−/Csf1r− mice were more severe than those of theCsf1op /Csf1op mice. The results indicate that all of the effects of CSF-1 are mediated via the CSF-1R, but that subtle effects of the CSF-1R could result from its CSF-1–independent activation.Keywords
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