Dual abnormal effects of mutant MITF encoded by <f>Miwh</f> allele on mouse mast cells: decreased but recognizable transactivation and inhibition of transactivation

MITF is a basic helix-loop-helix leucine zipper-type transcription factor and is important for development of mast cells. MITF encoded by <f>Miwh</f> allele (<f>Miwh</f>-MITF) was mutated at a single amino acid of basic domain, and possessed a deficient but apparent DNA-binding ability. Here, we characterized the unique effects of <f>Miwh</f>-MITF on the expression of mast cell-related genes. The expression level of mouse mast cell protease (mMCP)-4, -5, and -6 genes in <f>Miwh/Miwh</f> cultured mast cells (CMCs) was intermediate between levels of normal (+/+) CMCs and tg/tg CMCs, which did not express any MITFs. <f>Miwh</f>-MITF appeared to show the positive transactivation effect through the remaining DNA-binding ability. On the other hand, the expression level of tryptophan hydroxylase gene was lower in <f>Miwh/Miwh</f> CMCs than in tg/tg CMCs, suggesting the inhibitory effect of <f>Miwh</f>-MITF on the transactivation. <f>Miwh</f>-MITF possessed dual abnormal effects on transactivation of mast cell-related genes. [Copyright &y& Elsevier]