Loss of DNA binding ability of the transcription factor encoded by the mutant mi locus.

The mi locus of mice encodes a novel member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (MITF). Mutant mice of the mi/mi genotype have the deletion of an arginine in the basic domain and show the abnormality in development of eyes, melanocytes, osteoclasts and mast cells. The expression of the mast cell protease 6 (MMCP-6) gene is markedly reduced in mi/mi mice. We examined the in vitro binding ability of the normal and mutant MITF to a hexameric motif (CACATG) located in the 5'-flanking sequence of the MMCP-6 gene. The normal MITF bound the hexameric motif but the mutant MITF did not, suggesting that the MITF directly regulated the expression of the MMCP-6 gene.