Advances in Models of Fibrous Dysplasia/McCune-Albright Syndrome

The G_s G-protein coupled receptor pathway is a critical regulator of normal bone formation and function. The G_s pathway increases intracellular cAMP levels by ultimately acting on adenylate cyclase. McCune-Albright Syndrome (MAS) and fibrous dysplasia (FD) of the bone are two proto-typical conditions that result from increased cellular G_s signaling activity. Both are caused by somatic activating mutations in the GNAS gene that encodes for the G_sα subunit. FD bone lesions are particularly difficult to treat because of their variability and because of the lack of effective medical therapies. In this review, we briefly discuss the key clinical presentations of FD/MAS. We also review the current status of mouse models that target the G_s GPCR signaling pathway and human cellular models for FD/MAS. These powerful tools and our improving clinical knowledge will allow further elucidation of the roles of GPCR signaling in FD/MS pathogenesis, and facilitate the development of novel therapies for these medically significant conditions.