Liddle综合征是肾小管上皮钠通道（ENaC）基因突变引起的罕见病，可能与钠通道灭活障碍或开放频率增加有关，以青年、难治性高血压为特征，极易脑出血或早亡，预后差。本申课题组首次发现携带SCNN1G基因新突变Glu571stop的Liddle综合征家系，膜片钳预实验提示突变型细胞钠电流显著增加。但该突变位点的致病机制尚不明确，因此本课题组拟通过系列实验来揭示新突变的致病机制：①体外细胞实验：将野生型和突变型质粒转染至爪蟾卵母细胞，分别进行基因、蛋白质和细胞水平的机制探讨；②转基因大鼠实验：进行在体大鼠血压等指标检测和药物试验，以及离体大鼠肾小管上皮细胞的研究，并应用CRISPR-Cas9技术进行基因编辑修正，通过突变和突变修正的正反两方面实验探索机制。预期能明确该突变的致病机制，同时为高血压与ENaC的相关性研究提供理论依据，为离子通道病的机制研究提供模型，具有重要的理论意义和实用价值。

Liddle Syndrome is caused by the mutations in the gene encoding the renal tubular epithelial sodium channel, which may be related to the inactivation or an increase of opening frequency of sodium channels. It leads to hypertension resistant to routine anti-hypertension drug. Although with rare morbidity, it is usually identified youth onset and prone to cerebral hemorrhage and early death, the prognosis is very poor .The applicant recently found for the first time the novel mutation Glu571stop of SCNN1G gene in a Liddle Syndrome family and the preliminary data of patch clamp suggests that the Na+ current of the mutant cells is significantly increased compare to wild type cells. However, this mutation has not been reported so far, and the pathogenic mechanism is unclear. Therefore, this application aims to reveal the pathogenesis of the novel mutation in Liddle Syndrome by a series of experiments.1. In vitro: Constructing wild-type plasmids and Glu571stop mutant plasmids of SCNN1G gene, and transfecting into oocytes of xenopus to study SCNN1G in gene, protein and cell level; 2. In vivo: transgenic rats were developed, blood pressure and other related indicators and drug trials were performed; In vitro: rat renal tubular epithelial cells were modified by gene editing combined with CRISPR-Cas9 technology, both mutation and mutation modification experiments were carried out. It is expected that the study may clarify the pathogenic mechanism of the mutation and provide theoretical basis for the correlation between hypertension and ENaC .It is of great theoretical significance and practical value to provide a model for studying the mechanism of ion channel disease.