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Fgfr2+/P253R mouse model mimicking human Apert syndromes (AS) showed precocious closure of coronal sutures, premature of cranial base and dysmorphology of brain.Thus, abnormality in sutures, cranial base synchondroses and cerebrum may be responsible for skull malformation in Apert syndromes.In this study, we use Col2a1-cre, OC-cre, and Nestin-cre mice separately mating with Fgfr2+/P253R-neo mice to obtain cartilage, osteoblast, and brain-specific activated Fgfr2+/P253R mice and quantitatively compared the skull forms with their wildtype littermates using data from three-dimensional (3D) micro-CT and morphometric methods.Co12a1-253 mice skull also showed shortened skull dimensions along the rostrocaudal axis and broadened width of the frontal bone and craniofacial malformation with shortened nasal.Co12a1-253 mice also exhibited evidently advanced ossification of spheno-occipital synchondroses and basioccipital-exoccipital synchondroses.In OC-253 mice, the skull showed no significant gross morphology changes not in both 4-week and 8-week stage when compared with their wild-type littermates.Nestin253 mice showed increased width of neurocranium compared with their wild type littermates, whereas no obvious difference in length in total or part of skull.In conclusion, the results of our study indicate that AS is a combined result of the malformation in endochondral growth of the cranial base together with brain growth, and malformation in endochondral growth is a main reason.The premature synostosis of the coronal suture is possible affected by Fgfr2+/P253R in early stage of osteoblastic growth.whereas OC promoter is playing role in mature osteoblast, and thus, further study is needed to ensure if the premature of sutures were directly or not affected by Fgfr2+/P253R in osteoblastic tissue.These findings further provide some new clues for the future analyses of skull phenotypes and clinical management of AS.