CONSTITUTIVE EXPRESSION OF GSΑR201C IN MICE PRODUCES A HERITABLE, DIRECT REPLICA OF HUMAN FIBROUS DYSPLASIA BONE PATHOLOGY AND DEMONSTRATES ITS NATURAL HISTORY

J Bone Miner Res. 2014 Nov;29(11):2357-68. doi: 10.1002/jbmr.2267.

As in humans, FD lesions in mice developed only in the postnatal life; a defined spatial and temporal pattern characterized the onset and progression of lesions across the skeleton. In individual bones, lesions developed through a sequence of three distinct histopathological stages: a primary modeling phase defined by endosteal/medullary excess bone formation and normal resorption; a secondary phase, with excess, inappropriate remodeling; and a tertiary fibrous dysplastic phase, which reproduced a full-blown replica of the human bone pathology in mice of age ≥1 year. Gsα mutations are sufficient to cause FD, and are per se compatible with germline transmission and normal embryonic development in mice. Our novel murine lines constitute the first model of FD.