Characterization of M-CSF and its receptor in microphthalmic mice.

The macrophage colony-stimulating factor (M-CSF) gene expression in osteopetrotic mice (op/op) is defective due to a point-mutation in the M-CSF gene [1]. However, almost all osteopetrotic patients have been shown to have a normal or elevated circulating level of bioactive M-CSF [2]. To investigate the action of the M-CSF in mi/mi mice (microphthalmic; another osteopetrotic mouse mutant), M-CSF levels and its receptors were studied. We found that serum levels of M-CSF in mi/mi mice were not significantly different from normal control mice. The M-CSF receptor binding affinity of spleen-adherent cells was similar to that of control mice. In spleen cells from mi/mi mice, the receptor binding sites per cell (normalized to total spleen cells, M-CSF receptor positive cells, or M-CSF receptor RNA positive cells) were present in a greater number than in spleen cells from phenotypically normal siblings. Northern blot analysis showed that there is no significant difference in transcripts of the M-CSF receptor (c-fms) in the mi/mi and phenotypically normal mice. Unlike the op/op mutant, M-CSF levels, as well as the affinity and number of M-CSF receptors, do not explain the defect in osteoclastic function in the mi/mi mutation.