mi transcription factor (MITF) is important in regulating the differentiation of mast cells. In particular, MITF regulates the transcription of the mouse mast cell-specific serine protease (mMCP)-6 gene, which is generally expressed by the connective tissue-type of mast cells. In this study, we investigated alternative isoforms of MITF that regulate transcription of the mMCP-6 gene in bone marrow-derived cultured mast cells in mice. The expression of MITF isoforms was examined by RT-PCR. We observed that MITF-A, -E, -H and -Mc were expressed by mucosal-type mast cells cultured in the presence of IL-3, whereas the connective tissue-type mast cells cultured in the presence of stem cell factor (SCF) expressed MITF-A. Overexpression of MITF isoforms increased luciferase activity through the mMCP-6 promoter in NIH-3T3 cells and elevated the level of mMCP-6 expression in the MC/9 mast cell line. Moreover, mMCP-6 expression in mast cells was significantly inhibited by the depletion of MITF. The transcriptional activity and DNA binding of MITF-A was comparable to that of MITF isoforms, including MITF-E, -H, and -Mc. Our results therefore suggest that MITF-A may be an important isoform of MITF in regulating the transcription of mMCP-6 in mouse connective tissue mast cells.