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利用动物模型探索牙釉质发育不全中的釉原蛋白变体。

The use of animal models to explore amelogenin variants in amelogenesis imperfecta.

作者信息

Gibson Carolyn W, Kulkarni Ashok B, Wright J Timothy

机构信息

Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Cells Tissues Organs. 2005;181(3-4):196-201. doi: 10.1159/000091381.

DOI:10.1159/000091381
PMID:16612085
Abstract

Amelogenin proteins are secreted by ameloblast cells during tooth development. Because of extensive alternative splicing of the amelogenin primary RNA transcript, and because systematic proteolysis results in many additional peptides during enamel maturation, it has been difficult to assign function to individual amelogenins. Targeted deletions and transgenic mice have been generated in order to better understand amelogenin protein function in vivo. From these murine models, we have determined that amelogenins are responsible for normal enamel thickness and structure, but not for initiation of enamel mineral formation at the dentin-enamel junction. Although it is now clear that the amelogenin (AmelX) gene exists in a nested orientation and that AmelX is expressed at a low level in various developing tissues, the significance of these findings is incompletely understood. Future studies are expected to answer remaining questions concerning structure/function relationships among these 'enamel proteins'.

摘要

釉原蛋白是在牙齿发育过程中由成釉细胞分泌的。由于釉原蛋白初级RNA转录本存在广泛的可变剪接,并且在釉质成熟过程中系统性蛋白水解会产生许多额外的肽段,因此很难确定单个釉原蛋白的功能。为了更好地了解釉原蛋白在体内的功能,已构建了靶向缺失和转基因小鼠模型。从这些小鼠模型中,我们已确定釉原蛋白对正常釉质厚度和结构起作用,但对牙本质-釉质交界处釉质矿化的起始不起作用。虽然现在清楚釉原蛋白(AmelX)基因以嵌套方向存在,并且AmelX在各种发育组织中低水平表达,但这些发现的意义尚未完全了解。预计未来的研究将回答有关这些“釉质蛋白”结构/功能关系的剩余问题。

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The use of animal models to explore amelogenin variants in amelogenesis imperfecta.利用动物模型探索牙釉质发育不全中的釉原蛋白变体。
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引用本文的文献

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Splicing mutations in AMELX and ENAM cause amelogenesis imperfecta.剪接突变导致 AMELX 和 ENAM 引起釉质发育不全。
BMC Oral Health. 2023 Nov 20;23(1):893. doi: 10.1186/s12903-023-03508-8.
2
A N-Terminus Domain Determines Amelogenin's Stability to Guide the Development of Mouse Enamel Matrix.N 端结构域决定釉原蛋白的稳定性,从而指导小鼠牙釉基质的发育。
J Bone Miner Res. 2021 Sep;36(9):1781-1795. doi: 10.1002/jbmr.4329. Epub 2021 May 25.
3
Tooth enamel protein amelogenin binds to ameloblast cell membrane-mimicking vesicles via its N-terminus.
牙釉质蛋白釉原蛋白通过其N端与模拟成釉细胞细胞膜的囊泡结合。
Biochem Biophys Res Commun. 2015 Aug 28;464(3):956-61. doi: 10.1016/j.bbrc.2015.07.082. Epub 2015 Jul 17.
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A large X-chromosomal deletion is associated with microphthalmia with linear skin defects (MLS) and amelogenesis imperfecta (XAI).一个大的X染色体缺失与小眼症合并线性皮肤缺损(MLS)和牙釉质发育不全(XAI)相关。
Am J Med Genet A. 2009 Aug;149A(8):1698-705. doi: 10.1002/ajmg.a.32968.
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Synergistic roles of amelogenin and ameloblastin.釉原蛋白和成釉蛋白的协同作用。
J Dent Res. 2009 Apr;88(4):318-22. doi: 10.1177/0022034509334749.
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pH triggered self-assembly of native and recombinant amelogenins under physiological pH and temperature in vitro.在生理pH值和温度条件下,pH触发天然和重组牙釉蛋白在体外自组装。
J Struct Biol. 2007 Oct;160(1):57-69. doi: 10.1016/j.jsb.2007.06.007. Epub 2007 Jul 4.