title: Brain phenotypes in two FGFR2 mouse models for Apert syndrome.
abstract: Apert syndrome (AS) is one of at least nine disorders considered members of the fibroblast growth factor receptor (FGFR) -1, -2, and -3-related craniosynostosis syndromes. Nearly 100% of individuals diagnosed with AS carry one of two neighboring mutations on Fgfr2. The cranial phenotype associated with these two mutations includes coronal suture synostosis, either unilateral (unicoronal synostosis) or bilateral (bicoronal synostosis). Brain dysmorphology associated with AS is thought to be secondary to cranial vault or base alterations, but the variation in brain phenotypes within Apert syndrome is unexplained. Here, we present novel three-dimensional data on brain phenotypes of inbred mice at postnatal day 0 each carrying one of the two Fgfr2 mutations associated with AS. Our data suggest that the brain is primarily affected, rather than secondarily responding to skull dysmorphogenesis. Our hypothesis is that the skull and brain are both primarily affected in craniosynostosis and that shared phenogenetic developmental processes affect both tissues in craniosynostosis of Apert syndrome.
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri-School of Medicine, Columbia, Missouri 65212, USA. aldridgek@health.missouri.edu
authors.forename: Kristina
authors.initials: K
authors.lastname: Aldridge
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Hill
authors.forename: Jordan R
authors.initials: JR
authors.lastname: Austin
authors.forename: Christopher
authors.initials: C
authors.lastname: Percival
authors.forename: Neus
authors.initials: N
authors.lastname: Martinez-Abadias
authors.forename: Thomas
authors.initials: T
authors.lastname: Neuberger
authors.forename: Yingli
authors.initials: Y
authors.lastname: Wang
authors.forename: Ethylin Wang
authors.initials: EW
authors.lastname: Jabs
authors.forename: Joan T
authors.initials: JT
authors.lastname: Richtsmeier
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000196:embryology; D003398:Craniosynostoses / Q000235:genetics; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2