The Effects of Tissue-Nonspecific Alkaline Phosphatase Gene Therapy on Craniosynostosis and Craniofacial Morphology in the FGFR2C342Y/+ Mouse Model of Crouzon Craniosynostosis

摘要

ObjectivesCraniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue-nonspecific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs.