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

Xu Ming Dai, Gregory R. Ryan, Andrew J. Hapel, Melissa G. Dominguez, Robert G. Russell, Sara Kapp, Vonetta Sylvestre, E. Richard Stanley

Research output: Contribution to journalArticle

664 Scopus citations

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 cfms proto-oncogene. To investigate the in vivo specificity of CSF-1 for the CSF-1R, the mouse Csf1r gene was inactivated. The phenotype of Csf1-/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 both Csf1op/Csf1op and Csf1-/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 in Csf1r-/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 the Csf1r-/Csf1r- mice were more severe than those of the Csf1op/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.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalBlood
Volume99
Issue number1
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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