Beyond the closed suture in apert syndrome mouse models: evidence of primary effects of FGFR2 signaling on facial shape at birth.
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.
Martínez-Abadías
Neus
N
Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania 16803, USA.
Percival
Christopher
C
Aldridge
Kristina
K
Hill
Cheryl A
CA
Ryan
Timothy
T
Sirivunnabood
Satama
S
Wang
Yingli
Y
Jabs
Ethylin Wang
EW
Richtsmeier
Joan T
JT
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
C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2