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Proc Natl Acad Sci U S A. Jun 1990; 87(12): 4828–4832.

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


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.

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  • Marks SC, Jr, Lane PW. Osteopetrosis, a new recessive skeletal mutation on chromosome 12 of the mouse. J Hered. 1976 Jan-Feb;67(1):11–18. [PubMed]
  • Wiktor-Jedrzejczak WW, Ahmed A, Szczylik C, Skelly RR. Hematological characterization of congenital osteopetrosis in op/op mouse. Possible mechanism for abnormal macrophage differentiation. J Exp Med. 1982 Nov 1;156(5):1516–1527. [PMC free article] [PubMed]
  • Gisselbrecht S, Sola B, Fichelson S, Bordereaux D, Tambourin P, Mattei MG, Simon D, Guenet JL. The murine M-CSF gene is localized on chromosome 3. Blood. 1989 May 1;73(6):1742–1745. [PubMed]
  • MacDonald BR, Mundy GR, Clark S, Wang EA, Kuehl TJ, Stanley ER, Roodman GD. Effects of human recombinant CSF-GM and highly purified CSF-1 on the formation of multinucleated cells with osteoclast characteristics in long-term bone marrow cultures. J Bone Miner Res. 1986 Apr;1(2):227–233. [PubMed]
  • Hume DA, Pavli P, Donahue RE, Fidler IJ. The effect of human recombinant macrophage colony-stimulating factor (CSF-1) on the murine mononuclear phagocyte system in vivo. J Immunol. 1988 Nov 15;141(10):3405–3409. [PubMed]
  • Bartocci A, Pollard JW, Stanley ER. Regulation of colony-stimulating factor 1 during pregnancy. J Exp Med. 1986 Sep 1;164(3):956–961. [PMC free article] [PubMed]
  • Bradley TR, Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966 Jun;44(3):287–299. [PubMed]
  • Kelso A, Owens T. Production of two hemopoietic growth factors is differentially regulated in single T lymphocytes activated with an anti-T cell receptor antibody. J Immunol. 1988 Feb 15;140(4):1159–1167. [PubMed]
  • Dexter TM, Garland J, Scott D, Scolnick E, Metcalf D. Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980 Oct 1;152(4):1036–1047. [PMC free article] [PubMed]
  • Mosmann TR, Fong TA. Specific assays for cytokine production by T cells. J Immunol Methods. 1989 Jan 17;116(2):151–158. [PubMed]
  • Nicola NA, Metcalf D, Matsumoto M, Johnson GR. Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor. J Biol Chem. 1983 Jul 25;258(14):9017–9023. [PubMed]
  • Moore MA. G-CSF: its relationship to leukemia differentiation-inducing activity and other hemopoietic regulators. J Cell Physiol Suppl. 1982;1:53–64. [PubMed]
  • Stanley ER. Colony-stimulating factor (CSF) radioimmunoassay: detection of a CSF subclass stimulating macrophage production. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2969–2973. [PMC free article] [PubMed]
  • Stanley ER. The macrophage colony-stimulating factor, CSF-1. Methods Enzymol. 1985;116:564–587. [PubMed]
  • Ladner MB, Martin GA, Noble JA, Wittman VP, Warren MK, McGrogan M, Stanley ER. cDNA cloning and expression of murine macrophage colony-stimulating factor from L929 cells. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6706–6710. [PMC free article] [PubMed]
  • Pollard JW, Bartocci A, Arceci R, Orlofsky A, Ladner MB, Stanley ER. Apparent role of the macrophage growth factor, CSF-1, in placental development. Nature. 1987 Dec 3;330(6147):484–486. [PubMed]
  • Pojda Z, Szczylik C, Wiktor-Jedrzejczak W. Multiple lineage colony growth from human marrow in plasma clot diffusion chambers. Exp Hematol. 1987 Oct;15(9):922–927. [PubMed]
  • Bartocci A, Mastrogiannis DS, Migliorati G, Stockert RJ, Wolkoff AW, Stanley ER. Macrophages specifically regulate the concentration of their own growth factor in the circulation. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6179–6183. [PMC free article] [PubMed]
  • Minkin C. Bone acid phosphatase: tartrate-resistant acid phosphatase as a marker of osteoclast function. Calcif Tissue Int. 1982 May;34(3):285–290. [PubMed]
  • van de Wijngaert FP, Tas MC, van der Meer JW, Burger EH. Growth of osteoclast precursor-like cells from whole mouse bone marrow: inhibitory effect of CSF-1. Bone Miner. 1987 Nov;3(2):97–110. [PubMed]
  • Hattersley G, Dorey E, Horton MA, Chambers TJ. Human macrophage colony-stimulating factor inhibits bone resorption by osteoclasts disaggregated from rat bone. J Cell Physiol. 1988 Oct;137(1):199–203. [PubMed]
  • Arceci RJ, Shanahan F, Stanley ER, Pollard JW. Temporal expression and location of colony-stimulating factor 1 (CSF-1) and its receptor in the female reproductive tract are consistent with CSF-1-regulated placental development. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8818–8822. [PMC free article] [PubMed]

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