Enamel Structure Sophistication throuth Amelogenin Evolution

釉原蛋白进化带来的复杂牙釉质结构

基本信息

批准号：
7880098
负责人：
Tom Diekwisch
金额：
$ 38.86万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7880098
关键词：
Affect Amphibia Apatites Architecture Atomic Force Microscopy Biocompatible Materials Biological Assay Biological Models Biology Biomimetics Carbonates Cell Culture System Cell physiology Complex Cultured Cells Dental Enamel Development Electron Microscopy Enamel Formation Evolution Genes Glutamine Growth Human Hydroxyapatites In Vitro Knock-in Mouse Knock-out Knockout Mice Lead Mammals Mechanics Minerals Modeling Mus Organ Culture Techniques Pattern Phenotype Play Principal Investigator Proline Property Proteins Rana Reptiles Research Research Design Research Project Grants Role Running Solutions Structure Tandem Repeat Sequences Testing Thick Thinking Tooth structure Transgenic Mice Transgenic Model Transgenic Organisms amelogenin base biomineralization design in vitro Assay in vivo interest light scattering mineralization mouse model overexpression programs public health relevance repaired research study retinal rods self assembly

项目摘要

DESCRIPTION (provided by applicant): Tooth enamel consists of tightly packed carbonated hydroxyapatite crystals which are organized into rods (prisms) running obliquely to one another in alternating rows. This extraordinary 3D architecture is established during enamel development as a result of the coordinated activity of cellular processes and organic matrix secretion. The present proposal focuses on the role of the unique C-domain of the major enamel matrix gene product, amelogenin, as it pertains to enamel structural organization. In previous studies, we have documented a significant increase in amelogenin C-domain proline and glutamine tandem repeats and prismatic enamel organization during the amphibian/reptile to mammal transition. In the present application, we are using this evolutionary biology approach to decipher the role of the amelogenin C-domain in the evolution of complex enamel structure. As a first step, we have generated frog amelogenin- overexpressing mouse models featuring grossly altered enamel mineral organization and lack of prism formation. Enamel thickness was further decreased and prisms were lacking when amel-overexpressors were crossed with amel null mice. In order to understand how specific domains of the amelogenin gene might affect alterations in enamel biomineralization during vertebrate evolution, we are now submitting a research plan to determine the effect of amelogenin C-domain evolution as it relates to enamel matrix organization, enamel crystal and prism formation. Our studies are designed to test the hypothesis that complex mammalian enamel architecture is a result of enamel matrix structure sophistication facilitated by amelogenin C-domain evolution. PUBLIC HEALTH RELEVANCE: The purpose of this research project is to identify key factors in tooth enamel formation. Tooth enamel in frog teeth is thin, little organized, and soft, while tooth enamel in mammals' features sophisticated organization and is thicker and harder than frog enamel. Here we are comparing the difference between frog and mouse enamel to identify key differences in enamel formation on a protein level. We are interested in the center portion of the major enamel protein, amelogenin. We believe that this center portion plays an important role in enamel formation and we will use a number of models to find out whether our thinking is accurate. Among those model systems will be experiments in which we will mix this protein with crystal growth solutions and experiments in which we manipulate the major gene in mice. We hope that one day our approach will lead to new ways of repairing human teeth.

描述（由申请人提供）：牙齿搪瓷由紧密堆积的碳酸羟基磷灰石晶体组成，这些晶体被组织成杆（棱镜），在交替行中倾斜地倾斜。由于细胞过程和有机基质分泌的协调活性，这种非凡的3D体系结构是在搪瓷发育过程中建立的。本提案的重点是主要牙釉质基因产物Amelogenin的独特C域的作用，因为它与搪瓷结构组织有关。在先前的研究中，我们已经记录了在两栖动物/爬行动物到哺乳动物过渡期间，阿米他素C-蛋白蛋白蛋白蛋白酶脯氨酸和谷氨酰胺串联重复和棱镜搪瓷组织的显着增加。在本应用中，我们正在使用这种进化生物学方法来破译蛋白蛋白C-域在复杂搪瓷结构的演变中的作用。作为第一步，我们已经产生了青蛙氨基蛋白蛋白过表达的小鼠模型，这些模型具有严重改变的搪瓷矿物质组织和缺乏棱镜形成。当将Amel超过表达式与Amel Null小鼠交叉时，搪瓷厚度进一步减小，并且缺乏棱镜。为了了解椎间盘发展过程中氨基蛋白素基因的特定域如何影响搪瓷生物矿化的变化，我们现在正在提交一项研究计划，以确定与牙釉质基质组织，搪瓷晶体和棱镜形成相关的杏仁素C-域演化的效果。我们的研究旨在检验以下假设：复杂的哺乳动物牙釉质结构是酰胺蛋白C域的进化促进的搪瓷基质结构的结果。公共卫生相关性：该研究项目的目的是确定牙釉质形成中的关键因素。青蛙牙齿中的牙齿搪瓷薄，少，柔软，而哺乳动物的牙釉质具有复杂的组织，并且比青蛙搪瓷更厚，更坚硬。在这里，我们比较青蛙和小鼠搪瓷之间的差异，以识别蛋白质水平上搪瓷形成的关键差异。我们对主要搪瓷蛋白Amelogenin的中心部分感兴趣。我们认为，该中心部分在搪瓷形成中起着重要作用，我们将使用许多模型来找出我们的思维是否准确。在这些模型系统中，将是实验，我们将这种蛋白质与晶体生长溶液和实验混合在一起，并在其中操纵小鼠的主要基因。我们希望有一天我们的方法将导致修复人牙齿的新方法。