The incisors of rodents comprise an iron-rich enamel and grow throughout adult life, making them unique models of iron metabolism and tissue homeostasis during aging. Here, we deleted Atg7 (autophagy related 7) in murine ameloblasts, i.e. the epithelial cells that produce enamel. The absence of ATG7 blocked the transport of iron from ameloblasts into the maturing enamel, leading to a white instead of yellow surface of maxillary incisors. In aging mice, lack of ATG7 was associated with the growth of ectopic incisors inside severely deformed primordial incisors. These results suggest that 2 characteristic features of rodent incisors, i.e. deposition of iron on the enamel surface and stable growth during aging, depend on autophagic activity in ameloblasts.

Abbreviations: ATG5: autophagy related 5; ATG7: autophagy related 7; CMV: cytomegalovirus; Cre: Cre recombinase; CT: computed tomography; FTH1: ferritin heavy polypeptide 1; GFP: green fluorescent protein; KRT5: keratin 5; KRT14: keratin 14; LGALS3: lectin, galactose binding, soluble 3; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NCOA4: nuclear receptor coactivator 4; NRF2: nuclear factor, erythroid 2 like 2; SQSTM1: sequestosome 1.

啮齿动物的门牙包含富含铁的牙釉质，并在整个成年期生长，使它们成为衰老过程中铁代谢和组织稳态的独特模型。在这里，我们删除了鼠成釉细胞中的Atg7（自噬相关 7），即产生牙釉质的上皮细胞。ATG7 的缺失阻止了铁从成釉细胞转运到成熟的牙釉质中，导致上颌切牙表面呈白色而不是黄色。在衰老小鼠中，缺乏 ATG7 与严重变形的原始门牙内异位门牙的生长有关。这些结果表明啮齿动物门牙的两个特征，即铁在釉质表面的沉积和老化过程中的稳定生长，取决于成釉细胞的自噬活性。

缩写：ATG5：自噬相关5；ATG7：自噬相关7；CMV：巨细胞病毒；Cre：Cre 重组酶；CT：计算机断层扫描；FTH1：铁蛋白重多肽1；GFP：绿色荧光蛋白；KRT5：角蛋白 5；KRT14：角蛋白 14；LGALS3：凝集素，半乳糖结合，可溶性3；MAP1LC3/LC3：微管相关蛋白1轻链3；NCOA4：核受体辅激活因子4；NRF2：核因子，类红细胞2像2；SQSTM1：螯合体 1。