The craniofacial phenotype of the Crouzon mouse: analysis of a model for syndromic craniosynostosis using three-dimensional MicroCT.
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 Fgfr2(C342Y/+) 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 Fgfr2(C342Y/+) 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 Fgfr2(C342Y/+) mice as compared with wild-type littermates. Upper-jaw length was shorter in the Fgfr2(C342Y/+) mutant skulls, as was mandibular length.


CONCLUSIONS
Skulls of Fgfr2(C342Y/+) 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.
Perlyn
Chad A
CA
Division of Plastic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. cperlyn@molcool.wustl.edu
DeLeon
Valerie B
VB
Babbs
Christian
C
Govier
Daniel
D
Burell
Lance
L
Darvann
Tron
T
Kreiborg
Sven
S
Morriss-Kay
Gillian
G
D000818:Animals; D002508:Cephalometry; D003393:Cranial Sutures / Q000000981:diagnostic imaging; D003394:Craniofacial Dysostosis / Q000000981:diagnostic imaging* / Q000235:genetics; D003398:Craniosynostoses / Q000000981:diagnostic imaging* / Q000235:genetics; D004195:Disease Models, Animal; D005147:Facial Bones / Q000000981:diagnostic imaging*; D005624:Frontal Bone / Q000000981:diagnostic imaging; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008334:Mandible / Q000000981:diagnostic imaging; D008437:Maxilla / Q000000981:diagnostic imaging; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D009777:Occipital Bone / Q000000981:diagnostic imaging; D009915:Orbit / Q000000981:diagnostic imaging; D010294:Parietal Bone / Q000000981:diagnostic imaging; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D012886:Skull / Q000000981:diagnostic imaging*; D013100:Sphenoid Bone / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed / Q000379:methods*
D051497:Receptor, Fibroblast Growth Factor, Type 2