The Fgfr2 W290R mouse model of Crouzon syndrome

Childs Nerv Syst. 2012 Sep;28(9):1495-503. doi: 10.1007/s00381-012-1792-y. Epub 2012 Aug 8.

Abstract

Purpose: This study aimed to review and discuss the utility of the Fgfr2 (W290R) mouse mutant as a model of human Crouzon syndrome.

Methods: A review of current and past scientific literature on Fibroblast Growth Factor Receptor-2 (FGFR2) protein domain structure, FGFR mutations associated with human Crouzon syndrome, and phenotypic and molecular changes combined with recent observations and experimental data of the Fgfr2 (W290R) mouse mutant was conducted. A comparison of the Fgfr2 (W290R) mouse mutant with another mouse model of Crouzon syndrome, Fgfr2 (C342R) mouse mutant, was also performed. Finally, possible future research directions using the Fgfr2 (W290R) mutant mice were discussed.

Results: The Fgfr2 (W290R) heterozygous mouse exhibits defects characteristic of human Crouzon syndrome. At the molecular level, the defects observed in the mouse mutant are due to the dysregulation of signaling of both the IIIb and IIIc isoforms of Fgfr2. The involvement of the IIIb isoform of FGFR2 in the etiopathology of Crouzon syndrome is a novel finding in the craniosynostosis literature field. Dysregulated signaling of both IIIb and IIIc isoforms causes a broad spectrum of changes that explain some of the defects observed clinically in humans. Several of the defects observed in the Fgfr2 (W290R) homozygous mouse mutant are attributable to a loss-of-function mechanism in contrast to the frequently reported gain-of-function receptor function associated with mutated FGF receptors in craniosynostosis.

Conclusions: The Fgfr2 ( W290R ) mouse model can be used as a model system to further investigate the cellular, molecular, and biochemical mechanisms of Crouzon syndrome.

MeSH terms

  • Animals
  • Arginine / genetics*
  • Bone and Bones / pathology
  • Cartilage / pathology
  • Cranial Sutures / pathology
  • Craniofacial Dysostosis / genetics*
  • Craniofacial Dysostosis / pathology
  • Craniofacial Dysostosis / physiopathology*
  • Disease Models, Animal
  • Humans
  • Mice
  • Mutation / genetics*
  • Phenotype
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Tryptophan / genetics*

Substances

  • Tryptophan
  • Arginine
  • Fgfr2 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 2