Role of MITF for Mast Cell Differentiation Analyzed by Skin and Bone Marrow Transplantations

The basic helix-loop-helix leucine zipper transcription factor MITF is important for the development of mast cells. The mutant tg/tg mice, which do not express MITF, lack mast cells in tissues. For the development of mast cells, not only mast cell precursors but also environmental factors are necessary. The mutant W/Wv mice that also lack mast cells like tg/tg mice possess normal environment but abnormal mast cell precursors. Since MITF is expressed in both mast cells and tissues where mast cells develop, the tg/tg mice may show abnormalities in both mast cell precursor and tissue environment. We investigated the abnormalities of mast cell precursors and environment in tg/tg mice by skin and bone marrow transplantations. When bone marrow cells of tg/tg mice were transplanted to W/Wv mice, mast cells did not develop in tissues. The number of developing mast cells in the skin from W/Wv mice was much lower when grafted to tg/tg mice than when grafted to normal (+ / +) mice. These indicated that mast cell precursors of tg/tg mice did not develop in tissues. When bone marrow cells of + / + mice were transplanted, the number of developing mast cells was significantly lower in tg/tg mice than in W/Wv mice. When the skin was grafted to + / + mice, the magnitude of increase of mast cell number was lower in the graft from tg/tg mice than in the graft from W/Wv mice. These showed that the tissue environment for mast cell development was defective in tg/tg mice. MITF was essential for both mast cell precursors and tissue environment.