Korean J Orthod.
2006 Aug;36(4):284-294.
Craniofacial morphologic alteration induced by bone-targeted mutants of FGFR2 causing Apert and Crouzon syndrome
- Affiliations
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- 1Department of Orthodontics, College of Dentistry and Oral Science Research Center, Institute of Craniofacial Deformity, Yonsei University, Korea. orthojn@yumc.yonsei.ac.kr
- 2Department of Biochemistry, College of Dentistry, University of Pennsylvania, USA.
- 3Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, USA.
- 4Department of Orthodontics, College of Dentistry, Yonsei University, Korea.
Abstract
OBJECTIVE
Activating mutations in the fibroblast growth factor receptor-2 (FGFR2) have been shown to cause syndromic craniosynostosis such as Apert and Crouzon syndromes. The purpose of this pilot study was to investigate the resultant phenotypes induced by the two distinctive bone-targeted gene constructs of FGFR2, Pro253Arg and Cys278Phe, corresponding to human Apert and Crouzon syndromes respectively.
METHODS
Wild type and a transgenic mouse model with normal FGFR2 were used as controls to examine the validity of the microinjection. Micro-CT and morphometric analysis on the skull revealed the following results.
RESULTS
Both Apert and Crouzon mutants of FGFR2 induced fusion of calvarial sutures and anteroposteriorly constricted facial dimension, with anterior crossbite present only in Apert mice. Apert mice differed from Crouzon mice and transgenic mice with normal FGFR2 in the anterior cranial base flexure and calvarial flexure angle which implies a possible difference in the pathogenesis of the two mutations. In contrast, the transgenic mice with normal FGFR2 displayed normal craniofacial phenotype.
CONCLUSION
Apert and Crouzon mutations appear to lead to genotype-specific phenotypes, possibly causing the distinctive sites and sequence of synostosis in the calvaria and cranial base. The exact function of the altered FGFR2 at each suture needs further investigation.
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