title: Soluble form of FGFR2 with S252W partially prevents craniosynostosis of the apert mouse model.
abstract: BACKGROUND
  Apert syndrome (AS) is characterized by craniosynostosis, midfacial hypoplasia, and bony syndactyly. It is an autosomal dominantly inherited disease caused by point mutations (S252W or P253R) in fibroblast growth factor receptor (FGFR) 2. These mutations cause activation of FGFR2 depending on ligand binding. Recently, an AS mouse model, Fgfr2(+/) (S252W) , showed phenotypes similar to those of AS patients. We previously reported that the soluble form of FGFR2(S252W) (sFGFR2IIIc(S252W) ) efficiently inhibits enhanced osteoblastic differentiation caused by FGFR2 activation in AS in vitro, presumably because FGFs binding to FGFRs is interrupted. In this study, we developed Fgfr2(+/) (S252W) (Ap) mice expressing the sFGFR2IIIc(S252W) protein, and we investigated the effects of sFGFR2IIIc(S252W) on AS-like phenotypes.
  
  
  RESULTS
  In Ap mice, the coronal suture (CS) was fused prematurely at P1. In addition, the mice exhibited a widened interfrontal suture (IFS) with ectopic bone and thickened cartilage formation. In Fgfr2(+/) (S252W) sFGFR2IIIc(S252W) (Ap/Sol) mice, the CS was similar to that of wild-type mice. Ap/Sol mice did not show any ectopic bone or cartilage formation in the IFS, but showed a wider IFS than that of the wild-type mice.
  
  
  CONCLUSIONS
  sFGFR2IIIc(S252W) may partially prevent craniosynostosis in the Apert mouse model by affecting the CS and IFS in vivo.
authors.affiliation: Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Morita
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yukiho
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Chu-Xia
authors.initials: CX
authors.lastname: Deng
authors.forename: Noriko
authors.initials: N
authors.lastname: Funato
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
mesh_terms: D000168:Acrocephalosyndactylia / Q000196:embryology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D019943:Amino Acid Substitution; D000818:Animals; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000196:embryology / Q000473:pathology; D047108:Embryonic Development; D051379:Mice; D008817:Mice, Mutant Strains; D020125:Mutation, Missense; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism
chemical_list: C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Apert syndrome; craniofacial; osteogenesis; pharmacodynamics