Wright J T, Kiefer C L, Hall K I, Grubb B R
Department of Pediatric Dentistry, School of Dentistry, University of North Carolina at Chapel Hill 27599-7450, USA.
J Dent Res. 1996 Apr;75(4):966-73. doi: 10.1177/00220345960750041101.
Cystic fibrosis (CF) is a hereditary condition that affects cAMP-regulated chloride channels in epithelial tissues due to a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recently, a transgenic CF mouse model was developed at UNC that exhibits no CFTR expression. Interestingly, the CF mouse demonstrates abnormal incisor enamel. Therefore, the purpose of this investigation was to characterize the enamel in this CF mouse model. Incisors from CF and normal mice were evaluated by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The enamel proteins were examined by amino acid analysis, SDS-PAGE, and Western blot. Gross examination showed that 100% of CF mice had soft, chalky white incisor enamel, while the enamel of normal mice was hard and yellow-brown. LM indicated that the ameloblasts in the CF mice underwent premature degeneration shortly after completion of the secretory phase. The CF mouse enamel appeared to be of relatively normal thickness and showed a prism structure similar to that of normal mouse enamel. However, the CF mouse enamel crystallites appeared to have a rough granular surface compared with normal enamel. SDS-PAGE indicated that mature CF enamel retained low-molecular-weight material (approximately 20 kDa), whereas normal mature enamel did not. This low-molecular-weight material cross-reacted with anti-amelogenin antibodies in Western blot analysis. This investigation shows that abnormal CFTR expression in the mouse results in developmental abnormalities in the incisor enamel. Although further investigation is required to determine the mechanism leading to abnormal enamel formation, the CF mouse provides a potentially useful animal model for investigating aberrant enamel development.
囊性纤维化（CF）是一种遗传性疾病，由于囊性纤维化跨膜传导调节因子（CFTR）基因缺陷，影响上皮组织中受cAMP调节的氯离子通道。最近，北卡罗来纳大学开发了一种转基因CF小鼠模型，该模型不表达CFTR。有趣的是，CF小鼠的切牙釉质表现异常。因此，本研究的目的是对该CF小鼠模型中的釉质进行特征描述。通过光学显微镜（LM）、扫描电子显微镜（SEM）和透射电子显微镜（TEM）对CF和正常小鼠的切牙进行评估。通过氨基酸分析、SDS-PAGE和蛋白质免疫印迹法检测釉质蛋白。大体检查显示，100%的CF小鼠切牙釉质柔软、呈白垩色，而正常小鼠的釉质坚硬、呈黄褐色。LM显示，CF小鼠的成釉细胞在分泌期完成后不久就过早退化。CF小鼠的釉质厚度似乎相对正常，并且显示出与正常小鼠釉质相似的棱柱结构。然而，与正常釉质相比，CF小鼠的釉质微晶表面似乎粗糙且呈颗粒状。SDS-PAGE表明，成熟的CF釉质保留了低分子量物质（约20 kDa），而正常成熟釉质则没有。在蛋白质免疫印迹分析中，这种低分子量物质与抗釉原蛋白抗体发生交叉反应。本研究表明，小鼠中CFTR表达异常导致切牙釉质发育异常。尽管需要进一步研究以确定导致釉质形成异常的机制，但CF小鼠为研究异常釉质发育提供了一个潜在有用的动物模型。
