Molecular Genetics of Tooth Development

牙齿发育的分子遗传学

• 批准号: 6432052
• 负责人: Ashok B. KULKARNI
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6432052
• 关键词: ameloblasts; congenital dentition disorder; dental development; dentinogenesis; developmental genetics; disease /disorder model; embryonic stem cell; extracellular matrix; gene targeting; genetic promoter element; growth factor; laboratory mouse; molecular cloning; odontoblasts; osteogenesis imperfecta; transcription factor

Tooth development is a highly reguated process orchestrated by a number of genes that encode growth factors, transcription factors and extracellular matrix proteins. Molecular mechanisms underlying the noral and abnormal tooth development is not well characterized. We have initiated studies that focus on the candidate genes for the common tooth disorders such as dentinogenesis imperfecta (DGI), dentin dysplasia and osteognensis imperfcta as well as growth factor genes involved in tooth mineralization.Dentin sialophosphoprotein (DSPP) gene is a prime candidate for DGI-II. It encodes a non-collagenous protein that is specifically expressed in odontoblasts and ameloblasts during tooth development. We have clonedand characterized the murine DSPP homolog and targeted its locus mouse embryonic stem cells in order to generate a gene knockout model for DGI-II. Secondly, using the DSPP promoter we targeted expression of candidate genes in developing tooth to delineate their specific roles in tooth development. Studies are underway to characterize the - Dentinogenesis, molecular genetics, gene knockout, growth factors, extracellular matrix, mineralization

牙齿发育是一个高度调控的过程，由许多编码生长因子、转录因子和细胞外基质蛋白的基因精心策划。正常和异常牙齿发育的分子机制尚未得到很好的表征。我们已经启动了研究，重点关注常见牙齿疾病的候选基因，如牙本质发育不全（DGI）、牙本质发育不良和成骨不全以及与牙齿矿化有关的生长因子基因。牙本质唾液酸磷蛋白（DSPP）基因是主要候选基因DGI-II。它编码一种非胶原蛋白，在牙齿发育过程中在成牙本质细胞和成釉细胞中特异性表达。我们克隆并表征了小鼠 DSPP 同源物，并靶向其基因座小鼠胚胎干细胞，以生成 DGI-II 的基因敲除模型。其次，使用 DSPP 启动子，我们靶向发育牙齿中候选基因的表达，以描绘它们在牙齿发育中的特定作用。正在进行研究来表征 - 牙本质发生、分子遗传学、基因敲除、生长因子、细胞外基质、矿化