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: Xiaolan Du, Tujun Weng, Qidi Sun, Nan Su, Zhi Chen, Huabing Qi, Ming Jin, Liangjun Yin, Qifen He, Lin Chen
• Journal: Journal of anatomy (J Anat) Vol. 217 Issue 2 Pg. 97-105 (Aug 2010) ISSN: 1469-7580 [Electronic] England
• PMID: 20557404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fgfr2 protein, mouse
• Receptor, Fibroblast Growth Factor, Type 2

Topics

• Acrocephalosyndactylia (genetics, pathology, physiopathology)
• Aging (pathology)
• Animals
• Cephalometry (methods)
• Disease Models, Animal
• Facial Bones (growth & development, pathology)
• Gene Knock-In Techniques
• Mice
• Mice, Mutant Strains
• Mutation
• Receptor, Fibroblast Growth Factor, Type 2 (genetics)
• Skull (growth & development, pathology)