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：釉质和牙本质的蛋白质组学和遗传学：我们的目标是：