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A Ser252Trp [corrected] substitution in mouse fibroblast growth factor receptor 2 (Fgfr2) results in craniosynostosis.
Bone. 2003 Aug; 33(2):169-78.BONE

Abstract

Apert syndrome (AS) is one of the most severe craniosynostoses and is characterized by premature fusion of craniofacial sutures. Mutations of either Ser252Trp or Pro253Arg in fibroblast growth factor receptor 2 (FGFR2) are responsible for nearly all known cases of AS. Here we show that mutant mice carrying the activation mutation, Ser252Trp [corrected] which corresponds to Ser252Trp in human FGFR2, have malformations mimicking the skull abnormalities found in AS patients. Mutant mice (Fgfr2(250/+)) are smaller in body size with brachycephaly and exhibit distorted skulls with widely spaced eyes. Unexpectedly, the premature closure of the coronal suture is accompanied by decreased, rather than increased, bone formation. We demonstrate that the Fgfr2-Ser252Trp [corrected] mutation does not cause obvious alterations in cell proliferation and differentiation; however, it results in increased Bax expression and apoptosis of osteogenic cells in mutant coronal suture. The accelerated cell death possibly reduces the space between osteogenic fronts of flat bones and results in the physical contact of these bones. Thus, our data reveal that dysregulated apoptosis plays an important role in the pathogenesis of AS related phenotypes.

Authors+Show Affiliations

Genetics of Development and Disease Branch, NIDDK/NIH, 10/9N105, 10 Center Drive, Bethesda, MD 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14499350

Citation

Chen, Lin, et al. "A Ser252Trp [corrected] Substitution in Mouse Fibroblast Growth Factor Receptor 2 (Fgfr2) Results in Craniosynostosis." Bone, vol. 33, no. 2, 2003, pp. 169-78.
Chen L, Li D, Li C, et al. A Ser252Trp [corrected] substitution in mouse fibroblast growth factor receptor 2 (Fgfr2) results in craniosynostosis. Bone. 2003;33(2):169-78.
Chen, L., Li, D., Li, C., Engel, A., & Deng, C. X. (2003). A Ser252Trp [corrected] substitution in mouse fibroblast growth factor receptor 2 (Fgfr2) results in craniosynostosis. Bone, 33(2), 169-78.
Chen L, et al. A Ser252Trp [corrected] Substitution in Mouse Fibroblast Growth Factor Receptor 2 (Fgfr2) Results in Craniosynostosis. Bone. 2003;33(2):169-78. PubMed PMID: 14499350.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Ser252Trp [corrected] substitution in mouse fibroblast growth factor receptor 2 (Fgfr2) results in craniosynostosis. AU - Chen,Lin, AU - Li,Dan, AU - Li,Cuiling, AU - Engel,April, AU - Deng,Chu-Xia, PY - 2003/9/23/pubmed PY - 2004/5/25/medline PY - 2003/9/23/entrez SP - 169 EP - 78 JF - Bone JO - Bone VL - 33 IS - 2 N2 - Apert syndrome (AS) is one of the most severe craniosynostoses and is characterized by premature fusion of craniofacial sutures. Mutations of either Ser252Trp or Pro253Arg in fibroblast growth factor receptor 2 (FGFR2) are responsible for nearly all known cases of AS. Here we show that mutant mice carrying the activation mutation, Ser252Trp [corrected] which corresponds to Ser252Trp in human FGFR2, have malformations mimicking the skull abnormalities found in AS patients. Mutant mice (Fgfr2(250/+)) are smaller in body size with brachycephaly and exhibit distorted skulls with widely spaced eyes. Unexpectedly, the premature closure of the coronal suture is accompanied by decreased, rather than increased, bone formation. We demonstrate that the Fgfr2-Ser252Trp [corrected] mutation does not cause obvious alterations in cell proliferation and differentiation; however, it results in increased Bax expression and apoptosis of osteogenic cells in mutant coronal suture. The accelerated cell death possibly reduces the space between osteogenic fronts of flat bones and results in the physical contact of these bones. Thus, our data reveal that dysregulated apoptosis plays an important role in the pathogenesis of AS related phenotypes. SN - 8756-3282 UR - https://www.unboundmedicine.com/medline/citation/14499350/A_Ser252Trp_[corrected]_substitution_in_mouse_fibroblast_growth_factor_receptor_2__Fgfr2__results_in_craniosynostosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756328203002229 DB - PRIME DP - Unbound Medicine ER -