Ricerc@Sapienza

Fibrous Dysplasia of bone/McCune-Albright Syndrome (FD/MAS, OMIM#174800) is a disabling consequence of post-zygotic, gain-of-function mutations of the GNAS gene, encoding the alpha subunit of the stimulatory G protein, Gsa. FD represents the most severe and crippling aspect within the spectrum of skeletal, endocrine and cutaneous lesions that characterize the McCune-Albright syndrome, but also occurs (in association with the same mutations) in non-MAS patients as an isolated, monostotic or polyostotic disease. Current therapies for FD are merely palliative. The genetic nature of the disease calls for the development of radical therapeutic interventions based on gene correction or cell therapy, which, in turn, require the development of suitable experimental models of the disease. Capitalizing on the FD transgenic models that we have previously generated, we have recently developed a novel Immunodeficient/Fibrous Dysplasia (SCID/FD) transgenic mouse strain. Of note, this new mouse strain represents the first-in-class immunodeficient transgenic model of a human skeletal disease. In this project, we will first perform a detailed radiographic and histological analysis of the skeletal lesions of our new SCID/FD mice in comparison with those of FD mice. Then, we will use our SCID/FD mice for preliminary cell therapy studies for FD based on local transplantation of skeletal stem cells isolated from membrane-Tomato/membrane-GFP (mT/mG) dual fluorescent reporter mice.