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 FGFR2S252W (sFGFR2IIIcS252W) 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 sFGFR2IIIcS252W protein, and we investigated the effects of sFGFR2IIIcS252W 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 sFGFR2IIIcS252W (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: sFGFR2IIIcS252W may partially prevent craniosynostosis in the Apert mouse model by affecting the CS and IFS in vivo. © 2013 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.