TARGETED DISRUPTION OF THE BIGLYCAN GENE LEADS TO AN OSTEOPOROSIS-LIKE PHENOTYPE IN MICE

The resilience and strength of bone is due to the orderly mineralizati on of a specialized extracellular matrix (ECM) composed of type I coll agen (90%) and a host of non-collagenous proteins that are, in general , also found in other tissues. Biglycan (encoded by the gene Bgn) is a n ECM proteoglycan that is enriched in bone(1-3) and other non-skeleta l connective tissues. in vitro studies indicate that Bgn may function in connective tissue metabolism by binding to collagen fibrils(4) and TGF-beta (refs 5,6), and may promote neuronal survival(7). To study th e role of Bgn in vivo, we generated Bgn-deficient mice. Although appar ently normal at birth, these mice display a phenotype characterized by a reduced growth rate and decreased bone mass due to the absence of B gn. To our knowledge, this is the first report in which deficiency of a non-collagenous ECM protein leads to a skeletal phenotype that is ma rked by low bone mass that becomes more obvious with age. These mice m ay serve as an animal model to study the role of ECM proteins in osteo porosis.