Fgfr2 S252W突变小鼠下颌切牙改变的研究

Changes of mandibular incisor in Fgfr2 S252W mutant mice

目的对比野生型和成纤维细胞生长因子受体2(Fgfr2)基因S252W突变型小鼠下颌切牙表型的差异,探讨Fgfr2功能获得性突变对小鼠下颌切牙的影响。方法将EⅡa-Cre雄鼠与Fgfr2S252W-neo/+雌鼠交配,子代获得Fgfr2 S252W突变小鼠。在出生后56d(P56)取材进行Micro-CT、HE染色及钙黄绿素荧光双标检测,分别检测下颌切牙的大体形态、组织形态及牙齿矿化速率。结果新生突变小鼠即呈现出短颅畸形,56d时表现更为明显,Micro-CT显示突变小鼠的下颌切牙伸长及反畸形明显。HE染色显示突变小鼠成釉细胞、成牙本质细胞数目增多,形态多不规则,内釉上皮、外釉上皮形成的上皮隔皱缩。钙黄绿素荧光双标检测显示突变小鼠牙本质矿化生长速率明显高于对照小鼠。结论 Fgfr2S252W点突变对小鼠下颌切牙的伸长及反畸形有一定促进作用。

Objective To compare the phenotypic differences of mandibular incisor between the wild-type mice and fibroblast growth factor receptor 2 （Fgfr2） gene S252W mutant mice, and explore the influence of gain-of-function mutation in Fgfr2 gene on mandibular incisors in mice. Methods The male EⅡa-Cre mice were mated with Fgfr2S252W-neo/＋ females to obtain the Fgfr2 S252W mutant mice. On the 56th day after offspring＇s birth （P56）, samples were taken for Micro-CT, HE staining and calcein double fluorescent labeling to observe the gross appearance, tissue morphology and mineral apposition rate of mandibular incisors, respectively. Results The newborn mutant mice showed short cranial deformity, which became more obvious on P56. Micro-CT showed a significant elongation and cross-bite deformity of mandibular incisors. HE staining showed that there were more ameloblasts and odontoblasts in the mutant mice, mostly with irregular appearance; epithelial diaphragm composed of inner and outer enamel epithelium shrank. Calcein double fluorescent labeling showed that the mineral apposition rate of dentin in mutant mice was significantly higher than that in controls. Conclusion Fgfr2 S252W mutation accelerates the growth of mandibular incisors in mice, resulting in the elongation and cross-bite deformity of mandibular incisors.