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Study on the function of Tabby gene in tooth development

Tabby基因在牙齿发育中的功能研究

基本信息

批准号：
11694276
负责人：
KURISU Kojiro
金额：
$ 1.22万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11694276/
关键词：
Tabby mouse EDA model animal EGF EGF receptor Cell marker FGF

项目摘要

Tabby is a mouse mutant characterized by deficient development of the ectodermal organs : teeth, hair, and a subset of glands. Ectodysplasin, the protein encoded by the Tabby gene, was recently identified as a novel TNF-like transmembrane protein but little is known about its function. We have examined the Tabby tooth phenotype in detail by analysis of the adult and embryonic teeth. Tabby first molars had an obvious defect in cusp patterning as the number of cusps was reduced and the buccal and lingual cusps were joined. The disturbance in development was first visible morphologically in the bud stage molar. The primary enamel knot in a cap stage Tabby tooth expressed all enamel knot markers analyzed but was smaller than wild type and the first pair of developing secondary enamel knots was fused. We propose that the Tabby tooth phenotype is due to growth retardation during early stages of development which leads to reduced signaling from the primary enamel knot, followed by deficient growth of the dental epithelium and lack of formation of the last developing secondary enamel knots. The ectodysplasin transcripts were expressed in the outer enamel epithelium and dental lamina. When cultured in vitro Tabby bud/cap stage molars formed fewer cusps than wild-type controls. This phenotype was not rescued by exogenously added EGF despite the previously proposed link between Tabby and EGF.Instead FGF-10 partially restored morphogenesis and stimulated the development of additional tooth cusps in cultured Tabby molars.

猫是一种小鼠突变体，其特征是外胚层器官：牙齿、毛发和一部分腺体发育不足。猫编码的胞外异型蛋白是最近发现的一种新的肿瘤坏死因子样跨膜蛋白，但对其功能了解甚少。通过对成人牙齿和胚胎牙齿的分析，我们对猫牙齿的表型进行了详细的研究。猫第一磨牙牙尖数目减少，颊、舌尖结合，出现明显的牙尖缺陷。发育障碍最早出现在蕾状期磨牙的形态上。帽状期的原生釉质结猫牙表达了所分析的所有釉质结标记，但均小于野生型，第一对发育中的次生釉质结融合。我们认为，猫的牙齿表型是由于发育早期的生长迟缓导致初级釉质结发出的信号减少，随后牙齿上皮生长不足，最后发育中的次级釉质结缺乏形成。外异构体蛋白转录本在外釉上皮和牙板表达。与野生型对照相比，体外培养的猫芽/帽期磨牙形成的尖牙较少。这种表型不能通过外源性添加表皮生长因子来挽救，尽管先前认为猫和表皮生长因子之间存在联系，相反，成纤维细胞生长因子-10部分恢复了培养的猫磨牙的形态发生，并刺激了额外的牙尖发育。