title: Dynamic morphological changes in the skulls of mice mimicking human Apert syndrome resulting from gain-of-function mutation of FGFR2 (P253R).
abstract: Apert syndrome is caused mainly by gain-of-function mutations of fibroblast growth factor receptor 2. We have generated a mouse model (Fgfr2(+/P253R)) mimicking human Apert syndrome resulting from fibroblast growth factor receptor 2 Pro253Arg mutation using the knock-in approach. This mouse model in general has the characteristic skull morphology similar to that in humans with Apert syndrome. To characterize the detailed changes of form in the overall skull and its major anatomic structures, euclidean distance matrix analysis was used to quantitatively compare the form and growth difference between the skulls of mutants and their wild-type controls. There were substantial morphological differences between the skulls of mutants and their controls at 4 and 8 weeks of age (P < 0.01). The mutants showed shortened skull dimensions along the rostrocaudal axis, especially in their face. The width of the frontal bone and the distance between the two orbits were broadened mediolaterally. The neurocrania were significantly increased along the dorsoventral axis and slightly increased along the mediolateral axis, and also had anteriorly displayed opisthion along the rostrocaudal axis. Compared with wild-type, the mutant mandible had an anteriorly displaced coronoid process and mandibular condyle along the rostrocaudal axis. We further found that there was catch-up growth in the nasal bone, maxilla, zygomatic bone and some regions of the mandible of the mutant skulls during the 4-8-week interval. The above-mentioned findings further validate the Fgfr2(+/P253R) mouse strain as a good model for human Apert syndrome. The changes in form characterized in this study will help to elucidate the mechanisms through which the Pro253Arg mutation in fibroblast growth factor receptor 2 affects craniofacial development and causes Apert syndrome.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Center of Bone Metabolism and Repair, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Du
authors.forename: Tujun
authors.initials: T
authors.lastname: Weng
authors.forename: Qidi
authors.initials: Q
authors.lastname: Sun
authors.forename: Nan
authors.initials: N
authors.lastname: Su
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Huabing
authors.initials: H
authors.lastname: Qi
authors.forename: Ming
authors.initials: M
authors.lastname: Jin
authors.forename: Liangjun
authors.initials: L
authors.lastname: Yin
authors.forename: Qifen
authors.initials: Q
authors.lastname: He
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D000375:Aging / Q000473:pathology; D000818:Animals; D002508:Cephalometry / Q000379:methods; D004195:Disease Models, Animal; D005147:Facial Bones / Q000254:growth & development / Q000473:pathology; D055879:Gene Knock-In Techniques; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D012886:Skull / Q000254:growth & development / Q000473:pathology*
chemical_list: C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2