MICROPHTHALMIA (MI) IN MURINE MAST-CELLS - REGULATION OF ITS STIMULI-MEDIATED EXPRESSION ON THE TRANSLATIONAL LEVEL

Mice harboring a mutation in the microphthalmia (mi) gene display a va riety of abnormalities, including microphthalmia, depletion of skin me lanocytes, deafness, a defect in osteoclasts, and a major decrease in mast cell number and function. However, despite the possible critical role played by this protein in mast cell development and function, cha racterization of its mRNA and protein synthesis in these cells has not yet been performed. In this study, we investigated the regulation of the synthesis of mi in murine mast cells activated by various physiolo gic stimuli. Using a specific rabbit polyclonal anti-mi antibody, we f ound that interleukin-3, interleukin-C or aggregation of the mast cell high-affinity receptor for IgE (Fc epsilon RI) induced the synthesis of mi protein in these cells. None of these stimuli significantly affe cted the level of mi mRNA in the mast cells at any of the time points tested, Also, using this specific anti-mi antibody, an increase in mi protein synthesis was shown during differentiation of mast cells from their bone marrow cell precursors. Moreover, a complex containing mi b ound to upstream stimulating factor 2 was detected only in activated m ast cells. We conclude that the regulation of mi expression is on the translational level. Thus, stimulation of mast cells by a variety of s timuli elicits a signaling pathway that regulates mi expression. (C) 1 997 by The American Society of Hematology.