ENAMEL MATRIX SERINE PROTEINASE 1
牙釉质基质丝氨酸蛋白酶 1
基本信息
- 批准号:6697001
- 负责人:
- 金额:$ 19.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-09-01 至 2005-02-28
- 项目状态:已结题
- 来源:
- 关键词:amelogenin dental development dental disorder endopeptidases enzyme activity extracellular matrix proteins gene expression gene targeting genetically modified animals human tissue immunocytochemistry in situ hybridization laboratory mouse linkage mapping mass spectrometry normal ossification protein biosynthesis protein degradation protein metabolism secretory protein serine proteinases tooth enamel
项目摘要
Enamel matrix serine proteinase 1 (EMSP1) is proposed to process enamel proteins during the secretory stage, and degrade enamel proteins during the early maturation stage of amelogenesis. EMSP1 is believed to be critical for proper dental enamel formation and defects in the human EMSP1 gene are suspected of causing amelogenesis imperfecta. Two hypotheses are tested: l. EMSP1 function is essential for the correct processing of enamel matrix proteins during the secretory stage of enamel formation, and that a loss of function can result in hypoplastic enamel. 2. EMSP1 function is essential for the degradation of enamel matrix proteins during the transition/early maturation stages of enamel formation, and that a loss of function can result in hypommeralized enamel. The following 4 Specific.Aims are proposed to test these hypotheses: l. To determine the temporal and spatial expression of EMSP1 during the secretory. transition. and maturation stages of enamel biomineralization. In situ hybridization and immunohistochemistry will be performed on mouse maxillae and mandibles. The first and second molars and incisors will be analyzed from newborn, postnatal (PN) days 2, 4, 6, 8 and 14 and adult. 2. To characterize the enzymatic activity of EMSP1 on amelogenin. Recombinant pig amelogenin will be digested by recombinant pig EMSP1 in vitro. The digestion products will be characterized by Edman degradation and mass spectrometry and compared to amelogenin cleavage sites that occur in vivo. 3. To characterize enamel formation in the absence of mouse EMSP1 expression. EMSP1 knock-out mice will be generated and characterized. 4. To determine the genetic linkage of the human EMSP1 gene with inherited defects of dental enamel formation. In collaboration with 3 laboratories that have assembled large numbers of kindreds suffering for amelogenesis imperfecta (AI), a candidate gene approach will be used to establish linkage between the human EMSP1 gene and AI . Accomplishing these aims will gain important insights into the action of EMSP1 in the organization, processing, turnover, and degradation of enamel matrix proteins during enamel biomineralization.
釉质基质丝氨酸蛋白酶1(EMSP1)被认为在釉质形成的早期成熟阶段降解釉质蛋白,并在分泌阶段处理釉质蛋白。EMSP1被认为对牙釉质的正常形成至关重要,而人类EMSP1基因的缺陷被认为是导致釉质发生不完全的原因。对两个假说进行了检验:L认为,在釉质形成的分泌阶段,EMSP1的功能对于釉质基质蛋白的正确加工是必不可少的,并且功能的丧失会导致釉质发育不良。2.在釉质形成的过渡/早期成熟阶段,EMSP1功能对釉质基质蛋白的降解是必不可少的,功能丧失可导致釉质低聚集化。为了验证这些假说,我们提出了以下4个特例:L。确定EMSP1在分泌期的时间和空间表达。过渡。牙釉质生物矿化的成熟期。对小鼠上颌骨和下颌骨进行原位杂交和免疫组织化学染色。第一和第二磨牙和门牙将从新生儿、出生后2、4、6、8和14天以及成人进行分析。2.鉴定EMSP1对釉原蛋白的催化活性。重组猪釉原蛋白将在体外被重组猪EMSP1消化。消化产物将通过埃德曼降解和质谱学进行表征,并与体内发生的釉原蛋白裂解位点进行比较。3.研究小鼠EMSP1表达缺失时牙釉质形成的特点。将产生并鉴定EMSP1基因敲除小鼠。4.确定人EMSP1基因与牙釉质形成遗传性缺陷的遗传连锁关系。与聚集了大量成釉不全(AI)家系的3个实验室合作,将使用候选基因方法建立人类EMSP1基因与AI之间的连锁。实现这些目标将获得对EMSP1在釉质基质蛋白在釉质生物矿化过程中的组织、加工、周转和降解中的作用的重要见解。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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JAMES P SIMMER其他文献
JAMES P SIMMER的其他文献
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{{ truncateString('JAMES P SIMMER', 18)}}的其他基金
DSPP Function, Pathophysiology, and Genetic Diagnosis
DSPP 功能、病理生理学和遗传诊断
- 批准号:
10448405 - 财政年份:2018
- 资助金额:
$ 19.75万 - 项目类别:
Structural and Functional Analysis of Dentin Proteins
牙本质蛋白的结构和功能分析
- 批准号:
8197836 - 财政年份:2008
- 资助金额:
$ 19.75万 - 项目类别:
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 - 财政年份:2004
- 资助金额:
$ 19.75万 - 项目类别:
Proteomics 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:
7413624 - 财政年份:2004
- 资助金额:
$ 19.75万 - 项目类别:
Proteomics 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:
7779056 - 财政年份:2004
- 资助金额:
$ 19.75万 - 项目类别:
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