Factors affecting craniofacial development in a mouse model of Crouzon Syndrome Academic Article uri icon

abstract

  • Crouzon Syndrome (CS) is characterized by premature fusion of calvarial bones (craniosynostosis) as well facial malformations including midfacial hypoplasia and hypertelorism. The phenotype is variable, even when caused by the same mutation within the same family. The cause(s) of this variability remain unknown. Using a mouse model of CS, caused by a missense mutation in FGF Receptor 2, we investigate the role of age, sex, and parental genotype in the development of the craniofacial phenotype. Specimens were collected at E10.5?13.5, E17.5, P0, and at 12 weeks or more, andgenotyped. Specimens younger than 3 weeks were sexed using PCR for the SRY gene. 2D and 3D geometric morphometrics was used to compare craniofacial size and shape, using surface landmarks for embryos, and bones after birth. Wildtype and heterozygous groups were compared at each age, controlling for all other variables, to create a detailed picture of the ontogenetic progression of the CS phenotype caused by this mutation. Then, specimens were grouped by genotype and tested for differences in size and shape based on sex or parental genotypes. We identify when in development homozygous mutants, heterozygous mutants, and wildtype phenotyeps diverge in size and shape, and to what degree sex and parental genotypes affect the timing, severity, or variability of heterozygous and wildtype phenotypes at each age. Support or Funding Information Supported by NIH-NIDCR grants F32DE024939 to KB and 2R01DE018234-05A1 to RM and BH.

author list (cited authors)

  • Brakora, K., Percival, C. J., Green, R., Gong, S., Hallgrimsson, B., & Marcucio, R.

publication date

  • April 2016