Enamel Structure Sophistication throuth Amelogenin Evolution

牙釉质结构通过牙釉蛋白进化而变得复杂

• 批准号: 7840703
• 负责人: Tom Diekwisch
• 金额: $ 1.32万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7840703
• 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

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）：牙釉质由紧密堆积的碳酸化羟基磷灰石晶体组成，这些晶体组织成交替排列的相互倾斜的棒（棱柱）。这种非凡的3D结构是在釉质发育过程中建立的，这是细胞过程和有机基质分泌协调活动的结果。本建议的重点是独特的C-结构域的主要釉基质基因产物，釉原蛋白，因为它涉及到釉质结构组织的作用。在以前的研究中，我们已经记录了显着增加釉原蛋白C-结构域脯氨酸和谷氨酰胺串联重复序列和棱柱釉组织在两栖动物/爬行动物哺乳动物的过渡。在本申请中，我们使用这种进化生物学方法来破译釉原蛋白C结构域在复杂釉质结构进化中的作用。作为第一步，我们已经产生了青蛙釉原蛋白过表达小鼠模型，其特征是釉质矿物组织严重改变，缺乏棱柱形成。釉质厚度进一步减少，棱镜缺乏时，釉质过表达与釉质裸小鼠杂交。为了了解釉原蛋白基因的特定结构域如何影响脊椎动物进化过程中釉质生物矿化的改变，我们现在提交了一项研究计划，以确定釉原蛋白C-结构域进化的影响，因为它涉及到釉质基质组织，釉质晶体和棱镜的形成。我们的研究旨在验证这一假设，即复杂的哺乳动物釉质结构是釉原蛋白C结构域进化促进釉质基质结构复杂化的结果。 公共卫生相关性：本研究项目的目的是确定牙釉质形成的关键因素。青蛙牙齿的牙釉质很薄，几乎没有组织，而且很软，而哺乳动物的牙釉质具有复杂的组织，比青蛙的牙釉质更厚更硬。在这里，我们比较了青蛙和小鼠釉质之间的差异，以确定蛋白质水平上釉质形成的关键差异。我们感兴趣的是主要釉质蛋白质的中心部分，釉原蛋白。我们相信这个中心部分在牙釉质形成中起着重要作用，我们将使用一些模型来确定我们的想法是否准确。在这些模型系统中，我们将把这种蛋白质与晶体生长溶液混合的实验，以及我们操纵小鼠主要基因的实验。我们希望有一天，我们的方法将导致修复人类牙齿的新方法。