title: Beyond the closed suture in apert syndrome mouse models: evidence of primary effects of FGFR2 signaling on facial shape at birth.
abstract: Apert syndrome is a congenital disorder caused mainly by two neighboring mutations on fibroblast growth factor receptor 2 (FGFR2). Premature closure of the coronal suture is commonly considered the identifying and primary defect triggering or preceding the additional cranial malformations of Apert phenotype. Here we use two transgenic mouse models of Apert syndrome, Fgfr2(+/S252W) and Fgfr2(+/P253R), to explore variation in cranial phenotypes in newborn (P0) mice. Results show that the facial skeleton is the most affected region of the cranium. Coronal suture patency shows marked variation that is not strongly correlated with skull dysmorphology. The craniofacial effects of the FGFR2 mutations are similar, but Fgfr2(+/S252W) mutant mice display significantly more severe dysmorphology localized to the posterior palate. Our results demonstrate that coronal suture closure is neither the primary nor the sole locus of skull dysmorphology in these mouse models for Apert syndrome, but that the face is also primarily affected.
authors.affiliation: Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania 16803, USA.
authors.forename: Neus
authors.initials: N
authors.lastname: Martínez-Abadías
authors.forename: Christopher
authors.initials: C
authors.lastname: Percival
authors.forename: Kristina
authors.initials: K
authors.lastname: Aldridge
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Hill
authors.forename: Timothy
authors.initials: T
authors.lastname: Ryan
authors.forename: Satama
authors.initials: S
authors.lastname: Sirivunnabood
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 / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D003398:Craniosynostoses / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D012886:Skull / Q000033:anatomy & histology / Q000196:embryology
chemical_list: C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2