DSPP dosage affects tooth development and dentin mineralization.
DSPP dosage affects tooth development and dentin mineralization.
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DOI：
10.1371/journal.pone.0250429
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Ritchie HH
中科院分区：
文献类型：
--
作者：
Lim D;Wu KC;Lee A;Saunders TL;Ritchie HH
牙本质涎蛋白（DSP）和磷酸蛋白（PP）是牙本质中最主要的两种非胶原蛋白，它们是牙本质涎磷蛋白（DSPP）前体蛋白裂解的产物。DSPP基因敲除（KO）小鼠中DSPP基因的缺失导致与人类牙本质形成III型一致的特征。症状包括牙本质薄，牙髓腔变大，经常暴露牙髓，上皮-间质相互作用异常，牙髓中出现软骨细胞样细胞。为了更好地了解DSPP如何影响牙齿发育和牙本质形成，我们使用包含完整DSPP基因和启动子的细菌人工染色体转基因构建体（BAC-DSPP）在小鼠DSPP KO背景中直接产生BAC-DSPP转基因小鼠。产生并表征了两种BAC-DSPP转基因小鼠品系。BAC-DSPP菌株A切牙中的DSPP mRNA表达与野生型（wt）小鼠相似。BAC-DSPP品系B动物的DSPP mRNA表达仅为野生型小鼠的10%。菌株A切牙中的PP蛋白含量是野生型小鼠中发现的PP蛋白含量的25%，这足以完全挽救DSPP KO的矿物质密度缺陷，因为在出生后21天的动物磨牙中的microCT牙本质矿物质密度分析显示菌株A和野生型小鼠中的矿物质密度基本相同。具有5%PP表达的品系B小鼠切牙仅部分挽救了DSPP KO的矿物质密度缺陷，因为出生后21天的动物磨牙的microCT扫描表明与wt小鼠相比牙本质矿物质密度降低，尽管矿物质密度仍高于DSPP KO。此外，我们的研究结果表明，在上皮-间充质相互作用、成牙本质细胞谱系维持、沿着正常牙本质厚度和正常矿物质密度方面，菌株A中的DSPP剂量足以挽救DSPP KO缺陷，而菌株B中的DSPP基因剂量仅部分挽救上述DSPP KO缺陷。
Dentin Sialoprotein (DSP) and phosphophoryn (PP) are two most dominant non-collagenous proteins in dentin, which are the cleavage products of the DSPP (dentin sialophosphoprotein) precursor protein. The absence of the DSPP gene in DSPP knock-out (KO) mice results in characteristics that are consistent with dentinogenesis imperfecta type III in humans. Symptoms include thin dentin, bigger pulp chamber with frequent pulp exposure as well as abnormal epithelial-mesenchymal interactions, and the appearance of chondrocyte-like cells in dental pulp. To better understand how DSPP influences tooth development and dentin formation, we used a bacterial artificial chromosome transgene construct (BAC-DSPP) that contained the complete DSPP gene and promoter to generate BAC-DSPP transgenic mice directly in a mouse DSPP KO background. Two BAC-DSPP transgenic mouse strains were generated and characterized. DSPP mRNA expression in BAC-DSPP Strain A incisors was similar to that from wild-type (wt) mice. DSPP mRNA expression in BAC-DSPP Strain B animals was only 10% that of wt mice. PP protein content in Strain A incisors was 25% of that found in wt mice, which was sufficient to completely rescue the DSPP KO defect in mineral density, since microCT dentin mineral density analysis in 21-day postnatal animal molars showed essentially identical mineral density in both strain A and wt mice. Strain B mouse incisors, with 5% PP expression, only partially rescued the DSPP KO defect in mineral density, as microCT scans of 21-day postnatal animal molars indicated a reduced dentin mineral density compared to wt mice, though the mineral density was still increased over that of DSPP KO. Furthermore, our findings showed that DSPP dosage in Strain A was sufficient to rescue the DSPP KO defect in terms of epithelial-mesenchymal interactions, odontoblast lineage maintenance, along with normal dentin thickness and normal mineral density while DSPP gene dosage in Strain B only partially rescued the aforementioned DSPP KO defect.
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DOI：
10.1083/jcb.56.3.838
发表时间：
1973-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Weinstock M;Leblond CP
通讯作者：
Leblond CP
影响因子：
2.5
作者：
Chandler, Kelly J.;Chandler, Ronald L.;Mortlock, Douglas P.
通讯作者：
Mortlock, Douglas P.
影响因子：
--
作者：
LINDE, A
通讯作者：
LINDE, A
影响因子：
7.6
作者：
Lee, S. -Y.;Kim, S. -Y.;Kim, E. -C.
通讯作者：
Kim, E. -C.
影响因子：
7.8
作者：
WEINSTOCK, M;LEBLOND, CP
通讯作者：
LEBLOND, CP