A new study on mice has shown that the mutation in a gene called cartilage associated protein (CRTAP) can lead to osteogenesis imperfecta (OI), a condition that makes bones much more likely to break.
OI is considered to be a genetic disorder in the formation of collagen fibres, the protein framework of which bone and cartilage are built. Patients of the disease have a faulty gene that instructs their bodies to make either too little or weak collagen because of defects or mutations in one of the collagen genes.
In the new study, scientists have identified the gene, the mutation in which reduces the ability of a protein involved in collagen formation.
Dr. Brendan Boyce, professor of Pathology at the University of Rochester Medical Centre,said, “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.”
For their study, the researchers removed CRTAP gene in mice, and monitored for signs of abnormalities in them.
They found that the mice were unable to properly line up the fibres that make up collagen using an enzyme called 3-prolyl hydroxylase. As a result of the loss of normal 3-prolyl hydroxylase function, the cells that build bone (osteoblasts) were found to make thicker but fewer collagen fibres, resulting in weaker bone.
Boyce and his colleagues from the Centre for Musculoskeletal Research at the Medical Centre carried out microscopic analysis of bone cells of the genetically engineered mice. They found that in the absence of CRTAP, mice developed osteoporosis.
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.
However, the newly discovered gene is a recessive trait, signifying that the disease can be passed down generation to generation. The researchers say that when each parent has one mutated gene and one normal gene, they have one-in-four chance of having a child with OI.