Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1op/Csf1op) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis

Gregory R. Ryan, Xu Ming Dai, Melissa G. Dominguez, Wei Tong, Fenchi Chuan, Orin Chisholm, Robert G. Russell, Jeffrey W. Pollard, E. Richard Stanley

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161 Scopus citations

Abstract

Colony-stimulating factor 1 (CSF-1) regulates the survival, proliferation, and differentiation of mononuclear phagocytes. It is expressed as a secreted glycoprotein or proteoglycan found in the circulation or as a biologically active cell-surface glycoprotein. To investigate tissue CSF-1 regulation, CSF-1-null Csf1op/Csf1op mice expressing transgenes encoding the full-length membrane-spanning CSF-1 precursor driven by 3.13 kilobases of the mouse CSF-1 promoter and first intron were characterized. Transgene expression corrected the gross osteopetrotic, neurologic, weight, tooth, and reproductive defects of Csf1op/Csf1op mice. Detailed analysis of one transgenic line revealed that circulating CSF-1, tissue macrophage numbers, hematopoietic tissue cellularity, and hematopoietic parameters were normalized. Tissue CSF-1 levels were normal except for elevations in 4 secretory tissues. Skin fibroblasts from the transgenic mice secreted normal amounts of CSF-1 but also expressed some cell-surface CSF-1. Also, lacZ driven by the same promoter/first intron revealed β-galactosidase expression in hematopoietic, reproductive, and other tissue locations proximal to CSF-1 cellular targets, consistent with local regulation by CSF-1 at these sites. These studies indicate that the 3.13-kilobase promoter/first intron confers essentially normal CSF-1 expression. They also pinpoint new cellular sites of CSF-1 expression, including ovarian granulosa cells, mammary ductal epithelium, testicular Leydig cells, serous acinar cells of salivary gland, Paneth cells of the small intestine, as well as local sites in several other tissues.

Original languageEnglish (US)
Pages (from-to)74-84
Number of pages11
JournalBlood
Volume98
Issue number1
DOIs
StatePublished - Jul 1 2001

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Ryan, G. R., Dai, X. M., Dominguez, M. G., Tong, W., Chuan, F., Chisholm, O., Russell, R. G., Pollard, J. W., & Richard Stanley, E. (2001). Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1op/Csf1op) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis. Blood, 98(1), 74-84. https://doi.org/10.1182/blood.V98.1.74