REPRODUCTION OF HUMAN FIBROUS DYSPLASIA OF BONE IN IMMUNOCOMPROMISED MICE BY TRANSPLANTED MOSAICS OF NORMAL AND GS-ALPHA-MUTATED SKELETAL PROGENITOR CELLS

We have isolated progenitor cells from the stromal system of the fibro us dysplastic marrow of patients with McCune-Albright Syndrome. Analys is of the Gs alpha gene from individual colonies provided direct evide nce for the presence of two different genotypes within single fibrous dysplastic lesions: marrow stromal cells containing two normal Gs alph a alleles, and those containing one normal allele and an allele with a n activating mutation. Transplantation of clonal populations of normal cells into the subcutis of immunocompromised mice resulted in normal ossicle formation. in contrast, transplantation of clonal populations of mutant cells always led to the loss of transplanted cells from the transplantation site and no ossicle formation. However, transplantatio n of a mixture of normal and mutant cells reproduced an abnormal ectop ic ossicle recapitulating human fibrous dysplasia and providing an in vivo cellular model of this disease. These results provide experimenta l evidence for the necessity of both normal and mutant cells in the de velopment of McCune-Albright Syndrome fibrous dysplastic lesions in bo ne.