Proteomic and Genetics of Enamel and Dentin

牙釉质和牙本质的蛋白质组学和遗传学

• 批准号: 6873765
• 负责人: JAMES P SIMMER
• 金额: $ 33.82万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6873765
• 关键词: clinical research; dental development; dental disorder; dentin; developmental genetics; electrospray ionization mass spectrometry; extracellular matrix; extracellular matrix proteins; family genetics; gene mutation; genetic disorder; genetic screening; human subject; isoelectric point; patient oriented research; protein sequence; proteomics; swine; tooth enamel

DESCRIPTION: Proteomics and Genetics of Enamel and Dentin: Our goals are: a) to isolate and characterize proteins in the enamel and dentin matrices of developing teeth. b) to discover mutations in defective genes that cause dental disorders, and A proteomics approach is proposed to isolate and characterize proteins normally expressed during tooth formation. By discovering novel dentin and enamel matrix proteins, we will identify new candidate genes in the etiologies of inherited dental disorders, such as ame/ogenesis imperfecta (AI) and dentinogenesis imperfecta (DGI). Two Specific Aims are proposed: SA:1 Isolate and characterize molecules in the extracellular matrices of developing enamel and dentin; and dentin. SA 2: Identify genes and mutations that cause amelogenesis imperfecta and dentinogenesis imperfecta. In Specific Aim 1 we perform a comprehensive isolation and characterization of the protein components in developing enamel and dentin. Complete resolution of virtually every soluble matrix protein is achieved using a two-dimensional method that separates proteins first by isoelectric point and second by hydrophobicityo Isolated proteins are characterized by on-line electrospray ionization (ESI) time-of-flight mass spectrometry, by N-terminal sequencing, peptide mapping and characterization of posttranslational modifications. In Specific Aim 2 genetic studies are performed on kindreds having AI or DGI, using a candidate gene approach. The five candidate genes for autosomal AI (enamelin & ameloblastin on 4ql 1-q21, MMP-20 on 1lq22, tuftelin on lq21-31, and kallikrein-4 on 19ql 3.3-ql 3.4), the one candidate gene for X-linked AI (amelogenin on Xp22.3-p22.1), the two candidate genes for DGI (DSPP and DMP1 on 4q21), and candidate genes identified discovered in the Proteomics study will be tested for linkage to dental disease. This study will provide gene-based diagnostic criteria, improved genetic counseling, and lead to the development of novel prevention and therapeutic strategies for families suffering from inherited disease.

描述：搪瓷和牙本质的蛋白质组学和遗传学：我们的目标是： a）在发育的牙齿的搪瓷和牙本质矩阵中分离和表征蛋白质。 b）发现引起牙齿疾病的有缺陷基因的突变，以及 提出了一种蛋白质组学方法来分离和表征通常在牙齿形成过程中表达的蛋白质。通过发现新颖的牙本质和搪瓷基质蛋白，我们将在遗传牙科疾病的病因中鉴定新的候选基因，例如AME/OGENESIS IMPREFECTA（AI）和Dentinodenogeny Implosta（DGI）。 提出了两个具体目标： SA：1分离并表征了发育中的搪瓷和牙本质的细胞外基质中的分子；和牙本质。 SA 2：确定引起障碍的基因和突变，而牙本质发生不完美。 在特定的目标1中，我们在开发搪瓷和牙本质中对蛋白质成分进行了全面的隔离和表征。 Complete resolution of virtually every soluble matrix protein is achieved using a two-dimensional method that separates proteins first by isoelectric point and second by hydrophobicityo Isolated proteins are characterized by on-line electrospray ionization (ESI) time-of-flight mass spectrometry, by N-terminal sequencing, peptide mapping and characterization of posttranslational modifications. 在特定的目标中，使用候选基因方法对具有AI或DGI的亲属进行了2个遗传研究。常染色体AI的五个候选基因（4QL 1-Q21上的Enamelin＆Ameloblastin，1LQ22上的MMP-20，LQ21-31上的Tuftelin on tuftelin on 19ql 3.3-QL 3.4上的kallikrein-4），X-Linked Ai（ammelegent）x-linked ai（Amelegent）X-linked Anemegens xp22.322. 3.3-QL 3.4 DGI（4Q21上的DSPP和DMP1）以及在蛋白质组学研究中发现的候选基因将进行测试，以与牙齿疾病联系起来。 这项研究将提供基于基因的诊断标准，改善遗传咨询，并为患有遗传疾病的家庭的新型预防和治疗策略发展。