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目的通过定量分析模拟Apert综合征患者的FGFR2 Ser252Trp突变小鼠模型和野生型小鼠头颅表型,并与Apert患者所表现出来的异常头颅颜面特征进行比较,探讨所建立的Apert小鼠模型能否真实地模拟Apert综合征患者的头颅表型。方法采用蚂蚁啃食的方法制备Ser252Trp突变小鼠和同窝对照小鼠头颅标本,用三维坐标测量仪检测头颅27个标记点的三维坐标值,用欧几里德几何距离矩阵法(euclidean distance matrix analysis,EDMA)对突变小鼠和对照小鼠头颅三维数据进行处理和统计分析。结果Ser252Trp突变小鼠头颅形状与同窝对照组相比具有统计学差异(P<0.01),突变小鼠头颅长度缩短,且头颅前端缩短比后部缩短更严重,头颅面部鼻骨长度、前颌骨、上颌骨及颧骨长度明显缩短(P<0.01),眼间距和额骨宽度变宽,颅腔长度有所缩短,宽度增加,颅顶升高(P<0.01),这与Apert患者颅面的临床表现高度相似:眼间距增宽,面中部发育不良,鼻骨缩短,上颌骨发育低下,突眼,颅腔变宽呈圆鼓状。结论FGFR2 Ser252Trp突变小鼠从表型上真实地反映Apert患者的头颅颜面特征,可以作为人类Apert综合征的较好模型用于有关疾病致病机制、手术及药物治疗的研究模型。
Objective To quantitatively analyze the craniofacial phenotypes of FGFR2 Ser252Trp mutant mice and wild type mice with Apert syndrome and to compare with the abnormal craniofacial features of Apert patients to explore whether Apert mice model can be established True simulation of Apert syndrome in patients with head phenotype. Methods The skull specimens of Ser252Trp mutant mice and the littermate control mice were prepared by ants grazing. The three-dimensional coordinate values of 27 markers were detected by three-dimensional coordinate measuring instrument. The Euclidean distance matrix analysis, EDMA) were used to process and statistically analyze the cranial three-dimensional data of the mutant and control mice. Results The head shape of Ser252Trp mutant mice was significantly different from that of control group (P <0.01). The length of skull in mutant mice was shortened, and the shortening of the front of the skull was more severe than that of the back. The length of nasal bone in craniofacial region, (P <0.01). The distance between eyes and frontal bone broadened, the length of cranial cavity shortened, the width increased and the skull top increased (P <0.01), which was similar to that of Apert patients Highly similar clinical manifestations: widened interocular distance, surface dysplasia, shortening of the nasal bone, maxillary hypoplasia, exophthalmos, cranial cavity was widened. Conclusions FGFR2 Ser252Trp mutant mice can truly represent the facial features of Apert patients phenotypically and can be used as a good model of human Apert syndrome in the study of disease pathogenesis, surgery and drug therapy.