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

Abstract

The mi transcription factor (MITF) is a basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factor that is important for the development of mast cells. Mast cells ofmi/mi genotype express normal amount of abnormal MITF (mi-MITF), whereas mast cells of tg/tg genotype do not express any MITFs. 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 mice mutant allele (ce-MITF) lacks the Zip domain. We examined the importance of the Zip domain usingmice/micemice. The amounts of c-kit, granzyme B (Gr B), and tryptophan hydroxylase (TPH) messenger RNAs decreased in mast cells ofmice/mice mice to levels comparable 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 TPH is a rate-limiting enzyme for the synthesis of serotonin. The cytotoxic activity and serotonin content ofmice/mice mast cells were comparable to those of tg/tg mast cells and were significantly higher than those of mi/mi mast cells. The phenotype of mice/mice mast cells was similar to that of tg/tg mast cells rather than to that of mi/mi mast cells, suggesting that thece-MITF had no functions. The Zip domain of MITF appeared to be important for the development of mast cells.