"The study is important because it clarifies a new mechanism by which the OI can occur and makes possible new tests to identify affected children and provide them with added medical support."

"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."

Study Details
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 fibers 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, the cells that build bone (osteoblasts) were found to make thicker collagen fibers, but fewer of them, resulting in weaker bone.

Boyce and his group in the Center for Musculoskeletal Research at the Medical Center characterized 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. Another team working at McGill University in Montreal identified human patients who had OI due to mutations in CRTAP, demonstrating for the first time that CRTAP has an essential function in humans.