TY - JOUR T1 - Tissue nonspecific alkaline phosphatase improves bone quality but does not alleviate craniosynostosis in the FGFR2C342Y/+ mouse model of Crouzon syndrome JF - bioRxiv DO - 10.1101/526400 SP - 526400 AU - Hwa Kyung Nam AU - Sara Dean Schutte AU - Nan Hatch Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/01/21/526400.abstract N2 - Crouzon syndrome is a congenital disorder characterized by craniosynostosis, the premature fusion of cranial bones. Craniosynostosis leads to high intracranial pressure and abnormal skull and facial shapes that are relieved by surgery. Crouzon syndrome is caused by activating mutations in fibroblast growth factor receptor 2 (FGFR2). The goal of this study was to determine if delivery of recombinant tissue nonspecific alkaline phosphatase (TNAP) could prevent or diminish the severity of craniosynostosis in post-natal craniosynostosis onset BALB/c and/or peri-natal craniosynostosis onset C57BL/6 FGFR2C342Y/+ mouse models of Crouzon syndrome. Mice were injected with a lentivirus encoding a mineral targeted form of TNAP immediately after birth. Cranial bone fusion as well as cranial bone volume, mineral content and density were assessed by micro computed tomography. Craniofacial shape was measured with calipers using previously established landmarks and measurements. Alkaline phosphatase activity levels were measured in serum. Results show that postnatal delivery of TNAP increases serum levels of alkaline phosphatase activity and improves bone volume, density and mineral content, but does not alleviate craniosynostosis, craniofacial shape or cranial base abnormalities in FGFR2C342Y/+ Crouzon mice. These results indicate that post-natal recombinant TNAP enzyme therapy is therapeutic for bone mineralization but not efficacious for relief of FGFR-associated craniosynostosis and associated craniofacial shape defects. ER -