Beyond the Closed Suture in Apert Syndrome Mouse Models: Evidence of Primary Effects of FGFR2 Signaling on Facial Shape at Birth

被引:49
作者
Martinez-Abadias, Neus [1 ]
Percival, Christopher [1 ]
Aldridge, Kristina [2 ]
Hill, Cheryl A. [2 ]
Ryan, Timothy [1 ]
Sirivunnabood, Satama [1 ]
Wang, Yingli [3 ]
Jabs, Ethylin Wang [3 ]
Richtsmeier, Joan T. [1 ]
机构
[1] Penn State Univ, Dept Anthropol, University Pk, PA 16803 USA
[2] Univ Missouri, Sch Med, Dept Pathol & Anat Sci, Columbia, MO USA
[3] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA
基金
美国国家卫生研究院;
关键词
Apert syndrome; craniofacial shape; craniosynostosis; FGFR2; mouse model; suture; LIGAND-BINDING SPECIFICITY; BONE-DEVELOPMENT; CLEFT-PALATE; GROWTH; MUTATIONS; CRANIOSYNOSTOSIS; FEATURES; REVEALS; CROUZON; INACTIVATION;
D O I
10.1002/dvdy.22414
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
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. Developmental Dynamics 239:3058-3071, 2010. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:3058 / 3071
页数:14
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