Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse

Wieslaw Wiktor-Jedrzejczak, Anna Bartocci, Anthony W. Ferrante, Aftab Ahmed-Ansari, Kenneth W. Sell, Jeffrey W. Pollard, E. Richard Stanley

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Abstract

Osteopetrotic (op/op) mutant mice suffer from congenital osteopetrosis due to a severe deficiency of osteoclasts. Furthermore, the total number of mononuclear phagocytes is extremely low in affected mice. Serum, 11 tissues, and different cell and organ conditioned media from op/op mice were shown to be devoid of biologically active colony-stimulating factor 1 (CSF-1), whereas all of these preparations from littermate control +/+ and +/op mice contained the growth factor. The deficiency was specific for CSF-1 in that serum or conditioned media from op/op mice possessed elevated levels of at least three other macrophage growth factors. Partial correction of the op/op defect was observed following intraperitoneal implantation of diffusion chambers containing L929 cells, which in culture produce CSF-1 as their sole macrophage growth factor. No rearrangement of the CSF-1 gene in op/op mice was detected by Southern analysis. However, in contrast to control lung fibroblasts, which contained 4.6- and 2.3-kilobase CSF-1 mRNAs, only the 4.6-kilobase species was detected in op/op cells. An alteration in the CSF-1 gene is strongly implicated as the primary defect in op/op mice because they do not contain detectable CSF-1, their defect is correctable by administration of CSF-1, the op locus and the CSF-1 gene map within the same region of mouse chromosome 3, their CSF-1 mRNA biosynthesis is altered, and the op/op phenotype is consistent with the phenotype expected in a CSF-1 deficient mouse.

Original languageEnglish (US)
Pages (from-to)4828-4832
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number12
DOIs
StatePublished - Jan 1 1990

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Keywords

  • Macrophage deficiency
  • Macrophage growth factor
  • Mouse mutant
  • Osteopetrosis

ASJC Scopus subject areas

  • General

Cite this

Wiktor-Jedrzejczak, W., Bartocci, A., Ferrante, A. W., Ahmed-Ansari, A., Sell, K. W., Pollard, J. W., & Stanley, E. R. (1990). Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proceedings of the National Academy of Sciences of the United States of America, 87(12), 4828-4832. https://doi.org/10.1073/pnas.87.12.4828