@article{oai:niigata-u.repo.nii.ac.jp:00006443,
 author = {Naito, Makoto and Umeda, Syuji and Takahashi, Kiyoshi and Takatsuka, Hisakazu and Usuda, Hiroyuki and Ito, Shigeo and Umezu, Hajime and Shultz, Leonard D.},
 issue = {1},
 journal = {Acta medica et biologica, Acta medica et biologica},
 month = {Mar},
 note = {Macrophage colony-stimulating factor (M-CSF) or colony stimulating factor-1(CSF-1) functions as an important regulator of macrophage production, differentiation, and survival. This cytokine also plays an important local regulatory role in the uteroplacental unit during pregnancy. Ever since the osteopetrotic (op) mutation was demonstrated to be within the coding region of the CSF-1 structural gene itself, the op/op mouse has proved an important animal model for investigating the biological regulation of CSF-1. CSF-1-deficient op/op mice are severely monocytopenic and show marked reduction and defective differentiation of tissue macrophages. Impaired osteoclast differentiation results in osteopetrosis in the mutant mice. Most of the other tissue macrophage populations are reduced in number and are ultrastructurally immature. However, the degree of reduction in numbers of macrophages in the mutant mice varies among tissues, suggesting that the heterogeneity of macrophages is generated by their different dependency on CSF-1. After daily CSF-1 injections, the numbers of monocytes, tissue macrophages, and osteoclasts increased remarkably; these CSF-1-dependent macrophages showed morphological maturation. In contrast, the numbers of macrophages in the ovary, uterus, omentum, and synovial membrane were not increased. After glucan administration, Kupffer cells in op/op mice proliferated, transformed into epithelioid cells and multinucleated giant cells, and participated in low levels of granulomatous inflammation, but failed to show normal levels of granuloma formation. In CSF-1-treated op/op mice the process of granuloma formation was similar to that of normal littermates. These results indicate that CSF-1 is a potent inducer of the development and differentiation of CSF-1-dependent monocyte/macrophages and that CSF-1-independent macrophages also play an important role in granuloma formation. Thus, op/op mice serve as an excellent model system for clarifying the biological role of CSF-1 in physiological and pathological conditions.},
 pages = {1--11},
 title = {Osteopetrotic (op/op) Mice : An Animal Model for Investigating the Biology of Colony-stimulating Factor-1 (CSF-1/M-CSF)},
 volume = {44},
 year = {1996}
}