New Gene Responsible for Brittle Bone Disease Discovered -- MEDICA - World Forum for Medicine

The study found a new gene, that when mutated, reduces the ability of a protein involved in collagen formation, called CRTAP (cartilage-associated protein), to guide collagen production as it forms the proper framework of bone. "The study is important because it clarifies a new mechanism by which the osteogenesis imperfecta (OI) can occur and makes possible new tests to identify affected children and provide them with added medical support," Brendan Boyce, M.D. professor of Pathology at the University of Rochester Medical Center said. "There may be up to 15 percent of children with Brittle Bone Disease who have mutations related to the new gene. Although the number of affected children is small, the demonstration that they have an inherited form of OI could have a major impact on their future health and quality of life."

In the study, mice were genetically engineered by the Baylor team with the CRTAP gene removed, and then monitored for signs of abnormalities. Results showed that the mice were unable to properly line up the fibres that make up collagen using an enzyme called 3-prolyl hydroxylase, which they determined needs to bind to CRTAP for it to function normally. As a result of the loss of normal 3-prolyl hydroxylase function, osteoblasts were found to make thicker collagen fibres, but fewer of them, resulting in weaker bone.

Boyce and his group characterised the skeletal abnormalities in the genetically engineered mice and carried out studies of bone cells from the mice as well as detailed microscopic analysis of their bones. They found that, without this key gene, mice developed osteoporosis due to defects in their osteoblasts.; Source: University of Rochester Medical Center