Activating mutation of GS alpha in McCune-Albright syndrome causes skim pigmentation by tyrosinase gene activation on affected melanocytes

McCune-Albright syndrome (MAS) is a sporadic disease characterized by cafe- au-lait spots, polyostotic fibrous dysplasia and hyperfunctional endocrinop athies. To elucidate the mechanism of skin pigmentation, melanocytes, kerat inocytes and fibroblasts were primary cultured from the cafe-au-lait spot o f a MAS patient. Then, mutational analysis and morphologic evaluation were performed. Also, cAMP level and tyrosinase gene expression in cultured cell s were determined. Only Gsa mutation was found in affected melanocytes and the cAMP level in affected melanocytes was higher than that of normal melan ocytes, The mRNA expression of tyrosinase gene was increased in the affecte d melanocytes. This study suggests that skin pigmentation of MAS results fr om activating mutation of Gs alpha in melanocytes and the mechanism involve s the c-AMP-mediated tyrosinase gene activation. Copyright (C) 2000 S. Karg er AG, Basel.