Craniofacial anomalies in a murine model of heterozygous fibroblast growth factor 10 gene mutation.

Abstract

Dysregulation of Fibroblast Growth Factor 10 (FGF10), a member of the family of Fibroblast Growth Factor (FGF) proteins, has been implicated in craniofacial and dental anomalies, including craniosynostosis, cleft palate, and Lacrimo-Auriculo-Dento-Digital Syndrome. The aim of this murine study was to assess the craniofacial and dental phenotypes associated with a heterozygous FGF10 gene (FGF10+/- ) mutation at skeletal maturity. Skulls of 40 skeletally mature mice, comprising two genotypes (heterozygous FGF10+/- mutation, n = 22; wildtype, n = 18) and two sexes (male, n = 23; female, n = 17), were subjected to micro-computed tomography. Landmark-based linear dimensions were measured for the cranial vault, maxilla, mandible, and first molar teeth. Multivariate analysis of variance was performed to assess whether there were significant differences in the craniofacial and dental structures between genotypes and sexes. The craniomaxillary skeleton and the first molar teeth were smaller in the FGF10+/- mice (P < .05), but the mandible was unaffected. Sex did not have a significant effect on these structures (P > .05). Cranial sutural defects were noted in 5/22 (22.7%) mutant versus 2/18 (11.1%) wildtype mice, and cleft palate in only one (4.5%) mutant mouse. None of the mice displayed craniosynostosis, expansive bony lesions, bifid condyles, or impacted teeth. The FGF10+/- mutation was associated with craniomaxillary skeletal hypoplasia thatprobably arose from deficient (delayed) intramembranous ossification of the sutured bones. Overall, theskeletal and dental data suggest that the FGF10 gene plays an important role in the aetiology of craniofacial dysmorphology and malocclusion.