The Craniofacial Phenotype of the Crouzon Mouse: Analysis of a Model for Syndromic Craniosynostosis Using Three-Dimensional MicroCT

• Published in: The Cleft palate-craniofacial journal Vol. 43; no. 6; pp. 740 - 747
• Main Authors: Perlyn, Chad A., DeLeon, Valerie B., Babbs, Christian, Govier, Daniel, Burell, Lance, Darvann, Tron, Kreiborg, Sven, Morriss-Kay, Gillian
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.11.2006; American Cleft Palate-Craniofacial Association; SAGE PUBLICATIONS, INC
• Subjects: Animals; Biological and medical sciences; Cephalometry; Cranial Sutures - diagnostic imaging; Craniofacial Dysostosis - diagnostic imaging; Craniofacial Dysostosis - genetics; Craniosynostoses - diagnostic imaging; Craniosynostoses - genetics; Dentistry; Disease Models, Animal; Diseases of the osteoarticular system; Facial Bones - diagnostic imaging; Frontal Bone - diagnostic imaging; Genotype; Genotype & phenotype; Humans; Image Processing, Computer-Assisted - methods; Imaging, Three-Dimensional - methods; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Mandible - diagnostic imaging; Maxilla - diagnostic imaging; Medical disorders; Medical sciences; Mice; Mice, Mutant Strains; Mutation - genetics; Occipital Bone - diagnostic imaging; Orbit - diagnostic imaging; Otorhinolaryngology. Stomatology; Parietal Bone - diagnostic imaging; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Rodents; Skeletal system; Skull - diagnostic imaging; Sphenoid Bone - diagnostic imaging; Three dimensional imaging; Tomography, X-Ray Computed - methods; mouse model; fibroblast growth factor receptor; FGFR2; three-dimensional imaging; Crouzon syndrome; Fibroblast growth factor; Nervous system diseases; Stomatology; Craniosynostosis; Rodentia; Diseases of the osteoarticular system; Dysostosis; Vertebrata; Phenotype; Growth factor receptor; Mammalia; Mouse; Animal; Skull disease; Craniofacial; Models
• ISSN: 1055-6656; 1545-1569
• DOI: 10.1597/05-212

Objective: To characterize the craniofacial phenotype of a mouse model for Crouzon syndrome by a quantitative analysis of skull morphology in mutant and wild-type mice and to compare the findings with skull features observed in humans with Crouzon syndrome. Methods: MicroCT scans and skeletal preparations were obtained on previously described Fgfr2C342Y/+ Crouzon mutant mice and wild-type mice at 6 weeks of age. Three-dimensional coordinate data from biologically relevant landmarks on the skulls were collected. Euclidean Distance Matrix Analysis was used to quantify and compare skull shapes using these landmark data. Results: Obliteration of bilateral coronal sutures was observed in 80% of skulls, and complete synostosis of the sagittal suture was observed in 70%. In contrast, fewer than 40% of lambdoid sutures were found to be fully fused. In each of the 10 Fgfr2C342Y/+ mutant mice analyzed, the presphenoid-basisphenoid synchondrosis was fused. Skull height and width were increased in mutant mice, whereas skull length was decreased. Interorbital distance was also increased in Fgfr2C342Y/+ mice as compared with wild-type littermates. Upper-jaw length was shorter in the Fgfr2C342Y/+ mutant skulls, as was mandibular length. Conclusion: Skulls of Fgfr2C342Y/+ mice differ from normal littermates in a comparable manner with differences between the skulls of humans with Crouzon syndrome and those of unaffected individuals. These findings were consistent across several regions of anatomic interest. Further investigation into the molecular mechanisms underlying the anomalies seen in the Crouzon mouse model is currently under way.