Cartilage-associated Protein (CRTAP) Deficiency Causes Abnormal Craniofacial Bone Development in the Crtap^-/- Model of Osteogenesis Imperfecta

Objectives: Osteogenesis Imperfecta (OI) is most commonly associated with mutations in the genes encoding type I collagen. Mutations in genes for proteins involved in collagen processing and/or osteoblast function can also cause OI. Cartilage-associated protein (CRTAP) is responsible for the 3-hydroxylation of the alpha 1 chain of collagen type I. CTRAP functions to facilitate the posttranslational processes of chain recognition, chain assembly, folding of the triple helix, and also inhibits the inappropriate intracellular polymerization of collagen monomers into fibrils. Mutations in the gene for CTRAP cause forms of recessive osteogenesis imperfecta in humans that include craniofacial skeletal defects and craniosynostosis. Loss of CRTAP in mice causes an osteochondrodysplasia characterized by severe osteoporosis and decreased osteoid production. The aim of this study is to better understand how CRTAP influences craniofacial skeletal development, we are investigating Crtap^-/- mice to determine if they have a consistent craniofacial shape defect, abnormal cranial bones and/or abnormal maturation and growth of the cranial base.
Methods: Craniofacial shape abnormalities were quantified using digital calipers. Cranial bone, cranial suture and cranial base abnormalities were analyzed by micro CT and histomorphometry.
Results: Our results demonstrate that Crtap^-/- mice have a consistent craniofacial shape defect, in addition to abnormalities in cranial bone and cranial base bone quality and quantity.
Conclusions: Further understanding of mechanisms by which CRTAP influences craniofacial skeletal development could provide new targets for prevention of craniofacial shape defects and/or cranial base abnormalities in OI patients.