THE ROLE OR TYPE XXVII COLLAGEN IN SKELETOGENESIS

描述（由申请人提供）：

DESCRIPTION (provided by applicant): COL27A1 is a newly discovered gene that encodes a pro-alpha chain of type XXVII collagen. It is a member of the fibril-forming class of collagens, of which each member is linked to a disease of the skeletal, integumentary, or cardiovascular systems. COL27A1 is conserved through evolution and among human collagens, most closely resembles invertebrate fibrillar collagen genes, suggestive of an important biological function. Preliminary data indicate that COL27A1 is expressed primarily in cartilage, including the anlagen of bone, and in the eye and optic capsule. This pattern of expression is reminiscent of the type II and XI collagen genes, which when mutated result in forms of chondrodysplasia. Thus, we hypothesize that type XXVII collagen, like the other fibrillar collagens, is an essential component of the extracellular matrices (ECM) of these tissues, thereby making COL27A1 an excellent candidate locus for disorders in which abnormalities in chondrogenesis, and bone, ocular and otic development occur. To begin testing this hypothesis three specific aims will be accomplished. First, type XXVII collagen will be isolated from cultured rat chondrosarcoma cells and biochemically characterized in terms of its post-translational modifications and the nature of its trimeric molecule. Second, a developmentally specific tissue expression profile of COL27A1 will be determined by RT-PCR, in situ hybridization, and immunohistochemistry. Third, the location of type XXVII collagen in relation to other members of the extracellular matrix will be determined by immuno-gold electron microscopy, and by mass spectrometric analysis of cross-linked proteins. These studies are necessary to advance the field and will provide novel insights into the development of cartilaginous, skeletal, optic, and otic tissues. They will also pave the way for future investigations into the exact biological role of type XXVII collagen and its link to the pathogenesis of connective tissue diseases such as the spondyloepiphyseal and metaphyseal chondrodysplasias.