Craniosynostosis is the premature fusion of cranial bones. 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 a C57BL/6 FGFR2C342Y/+ model of neonatal onset craniosynostosis or a BALB/c FGFR2C342Y/+ model of postnatal onset craniosynostosis. 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., Alkaline phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST) activity levels were measured in serum. Neonatal delivery of TNAP diminished craniosynostosis severity from 94% suture obliteration in vehicle treated mice to 67% suture obliteration in treated mice, p<0.02) and the incidence of malocclusion from 82.4% to 34.7% (p<0.03), with no effect on cranial bone in C57BL/6 FGFR2C342Y/+ mice. In contrast, treatment with TNAP improved cranial bone volume (p< 0.01), density (p< 0.01) and mineral content (p< 0.01) but had no effect on craniosynostosis or malocclusion in BALB/c FGFR2C342Y/+ mice. , These results indicate that post-natal recombinant TNAP enzyme therapy diminishes craniosynostosis severity in the C57BL/6 FGFR2C342Y/+ neonatal onset mouse model of Crouzon syndrome, and that effects of exogenous TNAP are genetic background dependent., and Included in this collection is one set of images representing the C57BL/6 FGFR2C342Y/+ model of neonatal onset craniosynostosis, and one for the BALB/c FGFR2C342Y/+ model of postnatal onset craniosynostosis
Crouzon FGFR2-C342Y/+ and wild type littermate pups on a C57BL/6 congenic background were injected with lentivirus expressing recombinant TNAP enzyme or phosphate buffered saline shortly after birth. Mice were euthanized 3 weeks after birth for analyses.
Nam, H. K., Vesela, I., Schutte, S. D., & Hatch, N. E. (2020). Viral delivery of tissue nonspecific alkaline phosphatase diminishes craniosynostosis in one of two FGFR2C342Y/+ mouse models of Crouzon syndrome. PLOS ONE, 15(5), e0234073. https://doi.org/10.1371/journal.pone.0234073
