Tags

Type your tag names separated by a space and hit enter

Soluble form of FGFR2 with S252W partially prevents craniosynostosis of the apert mouse model.
Dev Dyn. 2014 Apr; 243(4):560-7.DD

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+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24259495

Citation

Morita, Jumpei, et al. "Soluble Form of FGFR2 With S252W Partially Prevents Craniosynostosis of the Apert Mouse Model." Developmental Dynamics : an Official Publication of the American Association of Anatomists, vol. 243, no. 4, 2014, pp. 560-7.
Morita J, Nakamura M, Kobayashi Y, et al. Soluble form of FGFR2 with S252W partially prevents craniosynostosis of the apert mouse model. Dev Dyn. 2014;243(4):560-7.
Morita, J., Nakamura, M., Kobayashi, Y., Deng, C. X., Funato, N., & Moriyama, K. (2014). Soluble form of FGFR2 with S252W partially prevents craniosynostosis of the apert mouse model. Developmental Dynamics : an Official Publication of the American Association of Anatomists, 243(4), 560-7. https://doi.org/10.1002/dvdy.24099
Morita J, et al. Soluble Form of FGFR2 With S252W Partially Prevents Craniosynostosis of the Apert Mouse Model. Dev Dyn. 2014;243(4):560-7. PubMed PMID: 24259495.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Soluble form of FGFR2 with S252W partially prevents craniosynostosis of the apert mouse model. AU - Morita,Jumpei, AU - Nakamura,Masataka, AU - Kobayashi,Yukiho, AU - Deng,Chu-Xia, AU - Funato,Noriko, AU - Moriyama,Keiji, Y1 - 2013/12/19/ PY - 2013/07/11/received PY - 2013/11/12/revised PY - 2013/11/17/accepted PY - 2013/11/22/entrez PY - 2013/11/22/pubmed PY - 2014/12/15/medline KW - Apert syndrome KW - craniofacial KW - osteogenesis KW - pharmacodynamics SP - 560 EP - 7 JF - Developmental dynamics : an official publication of the American Association of Anatomists JO - Dev. Dyn. VL - 243 IS - 4 N2 - 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. SN - 1097-0177 UR - https://www.unboundmedicine.com/medline/citation/24259495/Soluble_form_of_FGFR2_with_S252W_partially_prevents_craniosynostosis_of_the_apert_mouse_model_ L2 - https://doi.org/10.1002/dvdy.24099 DB - PRIME DP - Unbound Medicine ER -