IMPAIRED EXPRESSION OF INTEGRIN ALPHA-4 SUBUNIT IN CULTURED MAST-CELLS DERIVED FROM MUTANT MICE OF MI MI GENOTYPE/

The mi locus encodes a member of the basic-helix-loop-helix-leucine zi pper protein family of transcription factors (hereafter called MITF). We have reported that expression of several genes was impaired in cult ured mast cells (CMCs) of mi/mi mice due to a defective transactivatio n ability of mutant MITF (mi-MITF). Because attachment of mi/mi CMCs t o fibroblasts is impaired, we examined the expression of integrin gene s in mi/mi CMCs in the present study. Among the integrin genes examine d, the expression of integrin alpha 4 subunit was barely detectable in mi/mi CMCs, and the alpha 14 protein was not detected by flow cytomet ry either. The specific adhesion to vascular cell adhesion molecule-1 (VCAM-1), the ligand for alpha 4 subunit, was observed in +/+ CMCs but not in mi/mi CMCs, indicating that the expression of integrin alpha 4 subunit at a functional level did not occur in mi/mi CMCs. In the pro moter region of the alpha 4 subunit gene, there was a CACTTG motif to which normal MITF (+- MITF) bound. The coexpression of +-MITF but not of mi-MITF transactivated the promoter of the alpha 4 subunit gene. Th e deletion or mutation of the CACTTG motif abolished the transactivati on by +-MITF, suggesting that +-MITF directly transactivated the gene encoding alpha 4 subunit of integrin. (C) 1998 by The American Society of Hematology.