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Deformed Skull Morphology Is Caused by the Combined Effects of the Maldevelopment of Calvarias, Cranial Base and Brain in FGFR2-P253R Mice Mimicking Human Apert Syndrome
| Content Provider | Semantic Scholar |
|---|---|
| Author | Luo, Fengtao Xie, Yangli Xu, Wei Huang, Junlan Zhou, Siru Wang, Zuqiang Luo, Xiaoqing Liu, Mi Chen, Lin Du, Xiaolan |
| Copyright Year | 2017 |
| Abstract | Apert syndrome (AS) is a common genetic syndrome in humans characterized with craniosynostosis. Apert patients and mouse models showed abnormalities in sutures, cranial base and brain, that may all be involved in the pathogenesis of skull malformation of Apert syndrome. To distinguish the differential roles of these components of head in the pathogenesis of the abnormal skull morphology of AS, we generated mouse strains specifically expressing mutant FGFR2 in chondrocytes, osteoblasts, and progenitor cells of central nervous system (CNS) by crossing Fgfr2+/P253R-Neo mice with Col2a1-Cre, Osteocalcin-Cre (OC-Cre), and Nestin-Cre mice, respectively. We then quantitatively analyzed the skull and brain morphology of these mutant mice by micro-CT and micro-MRI using Euclidean distance matrix analysis (EDMA). Skulls of Col2a1-Fgfr2+/P253R mice showed Apert syndrome-like dysmorphology, such as shortened skull dimensions along the rostrocaudal axis, shortened nasal bone, and evidently advanced ossification of cranial base synchondroses. The OC-Fgfr2+/P253R mice showed malformation in face at 8-week stage. Nestin-Fgfr2+/P253R mice exhibited increased dorsoventral height and rostrocaudal length on the caudal skull and brain at 8 weeks. Our study indicates that the abnormal skull morphology of AS is caused by the combined effects of the maldevelopment in calvarias, cranial base, and brain tissue. These findings further deepen our knowledge about the pathogenesis of the abnormal skull morphology of AS, and provide new clues for the further analyses of skull phenotypes and clinical management of AS. |
| Starting Page | 32 |
| Ending Page | 45 |
| Page Count | 14 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.ijbs.com/v13p0032.pdf |
| Alternate Webpage(s) | http://www.ijbs.com/v13/p0032/ijbsv13p0032s1.pdf |
| PubMed reference number | 28123344v1 |
| Alternate Webpage(s) | https://doi.org/10.7150/ijbs.16287 |
| DOI | 10.7150/ijbs.16287 |
| Journal | International journal of biological sciences |
| Volume Number | 13 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Abnormality of the skull Apert syndrome Axis vertebra Base of skull structure Bone structure of cranium CNS disorder Caudal Chondrocyte Congenital Abnormality Contraceptives, Oral Cranial nerve diseases Craniosynostosis Dimensions FGFR2 protein, human Nasal bone structure Osteoblasts Osteocalcin Osteogenesis Patients Phenotype Surgical sutures nestin protein |
| Content Type | Text |
| Resource Type | Article |
