Keratin 4 regulates the development of human white sponge nevus
Keratin 4 regulates the development of human white sponge nevus
复制标题
角蛋白4调节人类白色海绵痣的发育
DOI：
10.1111/jop.12728
复制
发表时间：
2018-07-01
影响因子：
3.3
通讯作者：
Zhang，Xu
中科院分区：
文献类型：
--
作者：
Zhang，Jianming;Quan，Jingjing;Zhang，Xu
为探讨角蛋白4（keratin 4，KRT 4）基因在人白色海绵痣（white sponge nevus，WSN）发生中的作用，采用显微注射法将KRT 4野生型（wild‐type，WT）基因和E520 K突变基因分别转染pcDNA 3. 1载体，建立转基因小鼠模型。采用聚合酶链反应（PCR）和蛋白质印迹法对转基因建立者及其子代进行基因型鉴定。结果KRT 4转基因小鼠F1代口腔黏膜上皮细胞的阳性率为45.5%; 2月龄转基因小鼠中KRT 4蛋白的表达水平显著高于WT小鼠。此外，3月龄转基因小鼠的所有上皮层均显示KRT 4染色减少。表面和棘层充满透明细胞和泡状细胞，与WSN的临床症状相似。结论KRT 4基因突变可能在WSN的发病机制中起重要作用。
BackgroundThe aim of this study was to investigate the roles of keratin 4 (KRT4) gene in the development of human white sponge nevus (WSN).MethodsTransgenic mice were created using the microinjection method with pcDNA3.1 vectors expressing KRT4 wild‐type (WT) gene and E520K mutation. Polymerase chain reaction (PCR) and Western blotting were used to identify the genotype of transgenic founders and their filial generations. Expression of KRT4 in mouse oral mucosa was characterized by immunohistochemistry (IHC), and the whole epithelium layer of transgenic mice was observed using transmission electron microscope (TEM).ResultsThe positive rate of KRT4 transgenic mice in F1 generation was 45.5%. Expression level of KRT4 protein was significantly higher in 2‐month‐old transgenic mice than WT mice. Furthermore, all the epithelial lamina of 3‐month‐old transgenic mice showed reduced staining of KRT4. The surface and spinous layers were full of hyalocytes and bubble cells, which are similar to the clinical symptoms of WSN. For the ultrastructure, both tonofilaments and Odland bodies increased.ConclusionsOur study indicated the mutated KRT4 gene may play important roles in the pathogenesis of WSN.