Early craniofacial bone growth and maturation of Fgfr2+/P253R mice and littermates

Abstract

Our goal was to quantify the maturation of individual craniofacial bones and determine how the Fgfr2 P253R mutation modifies cranial bone maturation. Bone volumes and relative bone density histograms were measured from computed tomography images of Fgfr2+/P253R Apert craniosynostosis syndrome model mice and unaffected littermates at E15.5, E16.5, E17.5, P0, and P2. This data was used to quantify ontogenetic change in individual bone density and to test for differences in relative density between the two genotypes. Individual bones increase in volume and density at different rates across embryonic and perinatal development. While many bones of the Fgfr2+/P253R mice display larger volumes than those of littermates by P0, they generally display smaller volumes at P2. Relative bone density of the frontal and some facial/palatal bones is reduced for Fgfr2+/P253R mice at P2, but not before. These differences suggest a postnatal shift in the effect of the mutation on bone growth and maturation. Some of the most significant differences in craniofacial maturation between the two genotypes occur within the facial skeleton, identified as a region of significant dysmorphology in these mice and in humans carrying mutations for FGFR‐related craniosynostosis syndromes. Work supported in part by grants from the NSF to CJP (BCS‐1061554); the NIDCR/NIH and ARRA to JTR (R01DE018500; 3R01DE018500–02S1; R01DE022988).Grant Funding Source: NIDCR/NIH; NSF