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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR037042-02
Application #
3157897
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1986-08-01
Project End
1990-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033