肝细胞条件性Eva1a/Tmem166基因敲除小鼠的表型分析  

Phenotypic analysis of hepatocyte-specific Eva1a/Tmem166 gene knockout mice

作　　者：陈建宏 林欣[2] 冯金秋 丁鹏鹏 王苗苗 林琳[1] 刘红[1] 吴静[3] Chen Jianhong;Lin Xin;Feng Jinqiu;Ding Pengpeng;Wang Miaomiao;Lin Lin;Liu Hong;Wu Jing(Department of Gastroenterology,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;Peking University Center for Human Diseases Genomics,Beijing 100083,China;Department of Gastroenterology,Beijing Friendship Hospital,Capital Medical University,National Clinical Research Center for Digestive Diseases,Beijing Digestive Disease Center,Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京世纪坛医院消化内科,北京100038 [2]北京大学人类疾病基因研究中心,北京100083 [3]首都医科大学附属北京友谊医院消化内科国家消化系统疾病临床医学研究中心北京市消化疾病中心消化疾病癌前病变北京市重点实验室,北京100050

出　　处：《首都医科大学学报》2021年第4期568-574,共7页Journal of Capital Medical University

基　　金：国家自然科学基金(81900505);北京市医院管理中心“青苗”计划资助项目(QML20200702);北京世纪坛医院青年基金(2018-q09)。

摘　　要：目的应用Cre-LoxP技术构建自噬相关基因Eva1a肝细胞条件性敲除小鼠初步探讨Eva1a基因敲除对小鼠表型的影响。方法LoxP标记的Eva1a^(flox/+)小鼠与Alb-Cre工具鼠通过多次繁殖杂交,构建纯合型肝细胞条件性Eva1a基因敲除(Eva1a^(flox/flox):Alb-Cre)小鼠模型。选取Eva1a^(flox/flox):Alb-Cre小鼠与同窝野生(Eva1a^(flox/flox))小鼠雌雄进行体质量、肝指数、肝脏组织学、肝功能、糖脂代谢以及细胞自噬等表型分析。结果Eva1a纯合型基因敲除小鼠无胚胎致死现象,出生后一般生理状况良好。常规饲养条件下,肝脏Eva1a基因条件性敲除在小鼠体质量、肝脏外观以及组织结构、肝指数、肝功能、糖脂代谢及自噬等与野生型小鼠差异无统计学意义。结论肝细胞条件性Eva1a基因敲除对小鼠生理条件下的表型无显著影响,为进一步探讨Eva1a在肝脏疾病状态下的作用及分子机制提供了动物模型。Objective To construct mice models with hepatocyte-specific knockout of autophagy related gene Eva1 a using Cre-LoxP technique,and to preliminarily explore the effect of Eva1a gene knockout on the phenotype of mice.Methods LoxP-labeled Eva1a^(flox/+)mice and Alb-Cre mice were used to construct homozygous mice models with hepatocyte-specific Eva1 a gene knockout(Eva1a^(flox/flox):Alb-Cre)through multiple generations of hybridization.Eva1a^(flox/flox):Alb-Cre mice and Eva1 a^(flox/flox) mice were selected for phenotypic analysis,including body mass,liver index,liver histology,liver function,glycolipid metabolism,and autophagy level.Results There was no fetal death in homozygous Eva1a knockout mice,and no significant changes in the physiological condition were found.In conventional feeding conditions,hepatocyte-specific Eva1 a knockout had no significant difference in body weight,liver appearance,tissue structure,liver index,liver function,glucose and lipid metabolism,and autophagy level from wild-type mice.Conclusion Hepatocyte-specific Eva1 a gene knockout had no significant effect on the phenotype of mice in the physiological condition,and our study provided an animal model to further explore the role and molecular mechanism of Eva1 a in liver disease.

关 键 词：Eva1a/Tmem166 基因敲除 肝脏 表型 

分 类 号：R575[医药卫生—消化系统]