Importance of leucine zipper domain of mi transcription factor (MITF) for differentiation of mast cells demonstrated using mi(ce)/mi(ce) mutant mice of which MITF lacks the zipper domain

The mi transcription factor (MITF) is a basic helix-loop-helix leucine ripp er (bHLH-Zip) transcription factor that is important for the development of mast cells. Mast cells of mi/mi genotype express normal amount of abnormal Miff (mi-MITF), whereas mast cells of tg/tg genotype do not express any MI TFs. Mast cells of mi/mi mice show more severe abnormalities than those of tg/tg mice, indicating that the mi-MITF possesses the inhibitory function. The MITF encoded by the mi(ce) mutant allele (ce-MITF) lacks the Zip domain . We examined the importance of the Zip domain using mi(ce)/mi(ce) mice. Th e amounts of c-kit, granzyme B (Gr B), and tryptophan hydroxylase (TPH) mes senger RNAs decreased in mast cells of mi(ce)/mi(ce) mice to levels compara ble to those of tg/tg mice, and the amounts were intermediate between those of +/+ mice and those of mi/mi mice. Gr B mediates the cytotoxic activity of mast cells, and IPH is a rate-limiting enzyme for the synthesis of serot onin. the cytotoxic activity and serotonin content of mi(ce)/mi(ce) mast ce lls were comparable to those of tg/tg mast cells and were significantly hig her than those of mi/mi mast cells. The phenotype of mi(ce)/mi(ce) mast cel ls was similar to that of tg/tg mast cells rather than to that of mi/mi mas t cells, suggesting that the ce-MITF had no functions. The Zip domain of MI TF appeared to be important for the development of mast cells. (Blood. 2001 ;97:2038-2044) 2001 by The American Society of Hematology.