Truncated amelogenin and LRAP transgenes improve Amelx null mouse enamel.

Truncated amelogenin and LRAP transgenes improve Amelx null mouse enamel.
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截短的牙釉蛋白和 LRAP 转基因改善了 Amelx 缺失小鼠的牙釉质。

DOI:
10.1016/j.matbio.2015.11.005
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发表时间:
2016
期刊:
Matrix biology : journal of the International Society for Matrix Biology
影响因子:
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通讯作者:
Pugach,MeganK
Pugach,MeganK
中科院分区:
--
文献类型:
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作者:
Xia,Yan;Ren,Anna;Pugach,MeganK

文献摘要

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釉原蛋白是参与釉质矿化的最丰富的釉质蛋白。我们的目标是确定釉原蛋白的所有三个区域(N-末端,C-末端,中央核心)是否是釉质形成所必需的。釉原蛋白RNA是可变剪接的,在小鼠中产生至少16种不同的釉原蛋白同种型,其中M180和LRAP表达最丰富。在成釉细胞分泌后不久,M180被MMP 20切割,产生C-末端截短的(CTRNC)釉原蛋白。我们的目的是确定2个转基因(Tg),LRAP和CTRNC一起,是否可以改善LRAPTg/Amelx−/−和CTRNCTg/Amelx−/−釉质厚度和棱柱组织,这在Amelx −/−釉质中没有得到拯救。我们产生了CTRNCTg/LRAPTg/Amelx−/−小鼠,并通过microCT,SEM和显微硬度测试对发育和成熟的切牙和磨牙釉质进行了组织学分析。CTRNCTg和LRAPTg过表达共同显著改善了LRAPTg/Amelx−/−和CTRNCTg/Amelx−/−小鼠釉质的釉质表型,然而,仅当M180 Tg单独表达或与LRAPTg一起表达时,釉质显微硬度才恢复。我们确定,LRAP和CTRNC,共同表达釉原蛋白的所有三个区域(N-末端,C-末端和疏水核心)有助于最终的釉质厚度和棱镜组织在小鼠中。
Amelogenin is the most abundant enamel protein involved in enamel mineralization. Our goal was to determine whether all three regions of amelogenin (N-terminus, C-terminus, central core) are required for enamel formation. Amelogenin RNA is alternatively spliced, resulting in at least 16 different amelogenin isoforms in mice, with M180 and LRAP expressed most abundantly. Soon after secretion by ameloblasts, M180 is cleaved by MMP20 resulting in C-terminal truncated (CTRNC) amelogenin. We aimed to determine whether the 2 transgenes (Tg), LRAP and CTRNC together, can improve LRAPTg/Amelx−/− and CTRNCTg/Amelx−/− enamel thickness and prism organization, which were not rescued inAmelx−/− enamel. We generated CTRNCTg/LRAPTg/Amelx−/− mice and analyzed developing and mature incisor and molar enamel histologically, by microCT, SEM and microhardness testing. CTRNCTg and LRAPTg overexpression together significantly improved the enamel phenotype of LRAPTg/Amelx−/− and CTRNCTg/Amelx−/− mouse enamel, however enamel microhardness was recovered only when M180Tg was expressed, alone or with LRAPTg. We determined that both LRAP and CTRNC, which together express all three regions of the amelogenin protein (N-terminus, C-terminus and hydrophobic core) contribute to the final enamel thickness and prism organization in mice.