Osteogenesis imperfecta (OI) is a heterogenous group of heritable connective tissue disorders usually associated with bone fragility. Biochemical studies suggest that molecular defects of type I collagen are the root of the disorders. A wide variety of collagen abnormalities have been described but only a limited number of well defined molecular defects have been reported. We plan to study collagen defects in this disease by comparing the nature of the collagen structure, fibrillogenesis and the process of crosslinking in normal and effected bone and skin. The main objective in the proposal is to improve existing techniques for detecting minor defects in Osteogenesis imperfecta collagen by: 1. 2-D CNBr peptide mapping and reverse phase HPLC tryptic-mapping and finger printing of peptides recovered from the 2-D maps. 2. Measuring the thermal stability and the renaturability of procollagen synthesized by Osteogenesis imperfecta cells. 3. Examining the ability of Osteogenesis imperfecta collagen can form fibers and crosslinks as efficiently as the normal collagen. Finally, we will adapt these findings to improve the protocol for screening collagen defects in the prenatal diagnosis procedure for Osteogenesis imperfecta.
