MVK是我们用全基因组外显子测序和生物信息学技术，结合基因定位，筛选发现的播散性浅表性光化性汗孔角化症（Disseminated superficial actinic porokeratosis, DSAP)的致病基因。前期研究发现：MVK基因表达在角质形成细胞（KCs）氯化钙诱导的分化中发挥重要作用，且能阻止KCs的UVA诱导的凋亡，提示MVK突变可能导致KCs分化、凋亡等生理功能异常，但具体发病机制不明。本研究拟：通过构建野生型MVK和shRNA表达载体，转染HaCat细胞和原代KCs，建立MVK表达调控细胞模型，结合紫外线、甲羟戊酸途径中间代谢产物处理细胞模型，观察其中间产物对角质形成细胞增殖、分化和凋亡的影响，和对小G蛋白酯化及其相关途径的影响，并评判其可能的分子机制。MVK基因突变致DSAP的机制研究尚未见报道，本研究具有源头创新性，可为揭示DSAP发病机制、临床诊治提供帮助。

MVK is the causal gene of Disseminated superficial actinic porokeratosis (DSAP), which found by the whole exome sequencing, bioinformatics technology, and repoorted causal gene loci. Previous studies found that MVK gene expression play an important role in KCs differentiation induced by chloride, and could prevent UVA-induced apoptosis of KCs. The result point out MVK mutation may cause the dysfunction of KCs, such as differentiation and apoptosis, but the exact mechanism of the involvement of MVK in the pathogenesis of DSAP remains to be clarified.This study: we will construct the eukaryotic expression recombinant of MVK gene and shRNA vector targeting against MVK, then the recombninants will be transfected into HaCat cells and primary keratinocytes(KCs) to set up cell models with over or low MVK expression. The cells will be exposed to UV or added the mevalonate pathway intermediate metabolite, to analyze the affect of the intermediate metabolite on the proliferation, apoptosis and diffirentiation of KCs, and MVK expression and the intermediate metabolite on Small G protein esterification and relevant ways.Then explore the role of MVK in the pathogenesis of the DSAP. The mechanism research of DSAP caused by MVK mutation has not been reported, this research has original innovation. This study will lay foundation for revealing the pathogenesis, clinical diagnosis and treatment of DSAP.