ANIMAL-MODELS OF OSTEOPETROSIS - THE IMPACT OF RECENT MOLECULAR DEVELOPMENTS ON NOVEL STRATEGIES FOR THERAPEUTIC INTERVENTION

Osteopetrosis comprises a group of rare metabolic diseases of skeletal development that are characterized by a generalized increase in skele tal mass resulting from reduced osteoclast-mediated bone resorption. S pecific immune regulators and growth factors that influence osteoclast ontogeny and/or activation have been implicated in the pathogenesis o f some of the naturally occurring mutations associated with osteopetro sis in animals. Most recently, loss-of-function experiments using tran sgenic mice with targeted disruptions of the c-src or c-fos proto-onco genes have resulted in different osteoclast abnormalities that produce osteopetrosis. The information gained from these mutations in animals should continue to provide new understanding of the molecular defects associated with osteopetrosis, and to broader aspects of skeletal pat hology; this should result in more effective therapeutic intervention in humans.