Department of Oral Health Science, College of Dentistry, University of Kentucky, Lexington, Kentucky, USA.
Department of Neuroscience (Adjunct), School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA.
Clin Exp Dent Res. 2022 Oct;8(5):1185-1191. doi: 10.1002/cre2.612. Epub 2022 Jun 15.
The objective of this study is to confirm the developmental origin of the enamel organ and evaluate the role of E-cadherin in tooth development by conditional deletion in the oral epithelium and its enamel organ progeny. K5-Cre;ROSA26 compound mice were included in this study in order to confirm the oral epithelial origin of the enamel organ, as well as of the action of the K5-Cre transgene in ablating E-cadherin in the enamel organ. K5-Cre;Ecad knockout mice were included to evaluate the effects of the conditional E-cadherin ablation onto tooth development.
K5-Cre transgenic mice were crossed into the ROSA26 reporter mouse to trace the cell fate of the oral epithelium and its progeny in vivo. Moreover, K5-Cre mice were crossed into the Ecad mice to produce K5-Cre;Ecad compound mouse, as well as K5-Cre;Ecad and Ecad littermate controls. These litters were euthanized at postnatal day P2 to study the effects of conditional E-cadherin ablation in vivo.
The K5-Cre;ROSA26 compound mouse demonstrated that the origin of the enamel organ and the structures thereof are of oral epithelial origin. Furthermore, using the K5-Cre;Ecad compound mouse, we determined that conditional ablation of E-cadherin in the oral epithelium, and its progeny, results in dental anomalies involving elongation of the molar root, shrinkage of the pulp space, and alterations of the periapical area, including cementum hyperplasia. The K5-Cre;Ecad mice also displayed a smaller overall stature compared with heterozygotes and wild-type littermates.
E-cadherin is important in tooth development, including the formation of enamel, the crown, pulp space, and the roots.
本研究旨在通过口腔上皮及其牙釉器官祖细胞的条件性缺失，证实牙釉器官的发育起源，并评估 E-钙黏蛋白在牙齿发育中的作用。本研究纳入了 K5-Cre;ROSA26 复合小鼠，以确认牙釉器官以及 K5-Cre 转基因在牙釉器官中缺失 E-钙黏蛋白的作用的口腔上皮起源。纳入 K5-Cre;Ecad 敲除小鼠，以评估条件性 E-钙黏蛋白缺失对牙齿发育的影响。
将 K5-Cre 转基因小鼠与 ROSA26 报告小鼠杂交，以在体内追踪口腔上皮及其祖细胞的细胞命运。此外，将 K5-Cre 小鼠与 Ecad 小鼠杂交，以产生 K5-Cre;Ecad 复合小鼠，以及 K5-Cre;Ecad 和 Ecad 同窝对照小鼠。这些品系在出生后第 2 天处死，以研究体内条件性 E-钙黏蛋白缺失的影响。
K5-Cre;ROSA26 复合小鼠表明，牙釉器官及其结构起源于口腔上皮。此外，使用 K5-Cre;Ecad 复合小鼠，我们确定 E-钙黏蛋白在口腔上皮及其祖细胞中的条件性缺失导致涉及磨牙根伸长、牙髓腔缩小以及根尖区改变的牙齿异常，包括牙骨质增生。与杂合子和野生型同窝对照相比，K5-Cre;Ecad 小鼠的整体体型也较小。
E-钙黏蛋白在牙齿发育中很重要，包括釉质、牙冠、牙髓腔和牙根的形成。
