IADR Abstract Archives

Soluble FGFR2 with S252W prevents craniosynostosis of Apert model mouse

Introduction: Apert syndrome (AS) is characterized by craniosynostosis, midfacial hypoplasia, and bony syndactyly. It is an autosomal dominantly inherited disease caused by point mutation (S252W or P253R) in fibroblast growth factor receptor (FGFR) 2. These mutations raise constitutive activation of FGFR2 depending on ligand binding. Soluble forms of receptors have been reported as candidates for drug development in various fields, and we have previously reported that the soluble form of FGFR2-S252W (sFGFR2Ap) acts as an efficient inhibitor for the enhanced osteoblastic differentiation caused by FGFR2 activation in AS in vitro.

Objectives: To validate the effects of the sFGFR2Ap in a mouse model of Apert syndrome.

Methods: Mice carrying the sFGFR2-S252W transgene were crossed with EIIa-Cre mice to generate Ella-Cre; sFGFR2-S252W mice, and then crossed with Fgfr2Neo-S252W/+ mice to generate sFGFR2S252W; Fgfr2Neo-S252W/+; EIIa-Cre mice (Ap/Sol mice). We collected calvarial bones of Fgfr2Neo-S252W/+; EIIa-Cremice (Ap mice), and Ap/Sol mice at P1 for micro-CT examination and histological analysis. Bone mineral density (BMD) of calvarial bones was calculated by three-dimensional image-analysis software (TRI/3D-BON, Ratoc System Engineering). Coronal sutures (Cs) and interfrontal sutures (Ifs) were examined with Hematoxylin-Eosin staining, Alizarin Red staining, and Alcian Blue staining.

Results: There were no significant difference in BMD of calvarial bones of wild type (WT), Ap and Ap/Sol mice. In Ap mice (P1), the structure of the osteogenic front in Cs was irregular and seemed to be fusing prematurely, as reported previously. Additionally, they presented widened Ifs with ectopic bones. In Ap/Sol mice, the structure of coronal sutures was similar to WT mice. Ap/Sol mice did not show any ectopic bone in Ifs, while they showed wider Ifs than that of WT mice.

Conclusions: These data suggest that sFGFR2-S252W may potentially prevent craniosynostosis of Apert model mouse by affecting Cs and Ifs in vivo.

Division: Japanese Division Meeting
Meeting: 2012 Japanese Division Meeting (Niigata, Japan)
Location: Niigata, Japan
Year: 2012
Final Presentation ID:
Abstract Category|Abstract Category(s): Scientific Program
Authors
  • Morita, Jumpei  ( Tokyo Medical & Dental University, Tokyo, N/A, Japan )
  • Funato, Noriko  ( Tokyo Medical and Dental University, Tokyo, , Japan )
  • Kobayashi, Yukiho  ( Tokyo Medical & Dental University, Tokyo, N/A, Japan )
  • Nakamura, Masataka  ( Tokyo Medical and Dental University, Tokyo, , Japan )
  • Moriyama, Keiji  ( Tokyo Medical & Dental University, Tokyo, N/A, Japan )
  • SESSION INFORMATION
    Craniofacial Biology