Genetic Variations Related to Fluorosis Susceptibility

与氟中毒易感性相关的遗传变异

基本信息

批准号：
7569030
负责人：
Pamela K Den Besten
金额：
$ 19.31万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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：
2008-02-19 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7569030
关键词：
129P3/J Mouse A/J Mouse Accounting Acquired Dental Fluorosis Address Affect Ameloblasts Amelogenesis Appearance Biological Assay Candidate Disease Gene Cell Lineage Defect Dental Enamel Development Enamel Formation Exposure to Extracellular Matrix Fluorides Fracture Gene Expression Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Variation Goals Human Hydrolysis In Vitro Incisor Individual JUN gene Lasers Learning Luciferases MAPK8 gene MMP-20 Matrix Metalloproteinases Maturation-Stage Ameloblast Measures Microdissection Microscopy Minerals Mouse Strains Mus Nucleic Acid Regulatory Sequences Peptide Hydrolases Phosphorylation Population Population Study Predisposition Process Proteins Regulation Relative (related person)Reporter Genes Reporting Resistance Role Severities Staging Staining method Stains Testing Time Tissue-Specific Gene Expression Tooth structure amelogenin base drinking water early childhood fluorosis human population study mRNA Expression mouse model promoter response sound

项目摘要

DESCRIPTION (provided by applicant): Enamel fluorosis is a defect in enamel development seen after exposure to excess fluoride during tooth formation. Much remains to be learned about the mechanisms by which fluoride affects enamel formation, and in particular the effect of fluoride on ameloblast function. Studies of human populations and mouse strains suggest that a genetic component to individual susceptibility to enamel fluorosis. In these studies we will use mouse models known to be either fluoride sensitive (A/J) or fluoride resistant (129P3/J) to identify genes responsible for this variable response to fluoride. The overall hypothesis that will be tested in these studies is that enamel fluorosis results from factors that alter the relative levels of amelogenin and MMP-20 during enamel development. This hypothesis will be tested by the following Specific Aims. Specific Aim 1: To determine the correlation between the expression of the candidate genes and severity of fluorosed enamel in the A/J and 129P3/J mouse strains. Specific Aim 2: To determine whether fluoride differentially effects phosphorylation of JNK and cJun, in A/J and 129P3/J mouse strains. Specific Aim 3: To compare the regulatory regions of the amelogenin gene in both A/J and 129P3/J mouse strains and determine how the differences relate to susceptibility/resistance to Dental fluorosis. We will use laser microdissection microscopy to separate secretory and maturation stage ameloblasts from incisors of mice given fluoride in drinking water. Real-time PCR will be used to quantitate relative expression of amelogenin, MMP-20, and other candidate genes to identify variable response to fluoride in the genetically diverse mouse strains. Genetic differences in regulators of MMP-20 will be further investigated by measuring relative differences in JNK/c-Jun synthesis and phosphorylation in the two mouse models. Polymorphisms in the amelogenin gene will be investigated by comparing promoter sequences in the two mouse models. We anticipate that these studies will result in the identification of candidate genes that will form the basis an R01 application to further determine genetic susceptibility to fluorosis in humans.

描述（由申请人提供）：牙釉质氟斑牙是牙齿形成过程中暴露于过量氟化物后出现的牙釉质发育缺陷。关于氟化物影响牙釉质形成的机制，特别是氟化物对成釉细胞功能的影响，还有很多有待了解。对人群和小鼠品系的研究表明，个体对牙釉质氟中毒的易感性存在遗传因素。在这些研究中，我们将使用已知对氟化物敏感（A/J）或氟化物抗性（129P3/J）的小鼠模型来鉴定负责这种对氟化物的可变反应的基因。这些研究将检验的总体假设是，牙釉质氟中毒是由改变牙釉质发育过程中釉原蛋白和 MMP-20 相对水平的因素引起的。该假设将通过以下具体目标进行检验。具体目标 1：确定 A/J 和 129P3/J 小鼠品系中候选基因的表达与氟牙釉质严重程度之间的相关性。具体目标 2：确定氟化物是否对 A/J 和 129P3/J 小鼠品系中的 JNK 和 cJun 磷酸化产生差异影响。具体目标 3：比较 A/J 和 129P3/J 小鼠品系中牙釉蛋白基因的调控区域，并确定差异与氟斑牙易感性/抵抗力之间的关系。我们将使用激光显微切割显微镜从在饮用水中给予氟化物的小鼠的门牙中分离分泌和成熟阶段的成釉细胞。实时 PCR 将用于定量牙釉蛋白、MMP-20 和其他候选基因的相对表达，以确定遗传多样性小鼠品系对氟化物的可变反应。通过测量两种小鼠模型中 JNK/c-Jun 合成和磷酸化的相对差异，将进一步研究 MMP-20 调节因子的遗传差异。将通过比较两种小鼠模型中的启动子序列来研究牙釉蛋白基因的多态性。我们预计这些研究将鉴定出候选基因，这些基因将成为 R01 应用的基础，以进一步确定人类对氟中毒的遗传易感性。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

articleDifferentiation potential of STRO-1 + dental pulp stem cells changes during cell passaging

开放获取研究文章 Stro-1 牙髓干细胞的分化潜能在细胞传代过程中发生变化

DOI：
发表时间：
2024-09-13
期刊：
影响因子：
0
作者：
Jinhua Yu;Huixia He;Chunbo Tang;Guangdong Zhang;Yuanfei Li;Ruoning Wang;Jun;Yan Jin
通讯作者：
Yan Jin

氟化物相关的行为结果变化可能与血清素增加有关。

DOI：
发表时间：
2019
期刊：
影响因子：
2.9
作者：
Lu, Fuxin;Zhang, Yan;Trivedi, Alpa;Jiang, Xianging;Chandra, Dave;Zheng, Jiaolin;Nakano, Yukiko;Abduweli Uyghurturk, Dawud;Jalai, Rozita;Onur, Sirin Guner;Mentes, Ali;DenBesten, Pamela K
通讯作者：
DenBesten, Pamela K

Characterization of primary dental pulp cells in vitro.

原代牙髓细胞的体外表征。