瘦素基因敲除小鼠模型的建立及表型分析

摘要

目的 建立瘦素(Lep)基因敲除小鼠模型并对相关表型进行分析,为肥胖和糖尿病相关研究和药物研发提供动物模型.方法 采用小鼠胚胎干细和同源重组方法,建立Lep基因敲除小鼠模型,分别对Lep基因敲除三种基因型小鼠体质量、血糖的变化情况,血清胰岛素以及肝功能、肾功能、血脂等血液生化指标变化情况进行比较分析;对纯合子和野生型小鼠的肝脏、肾脏进行了病理学检测.结果 对构建的Lep基因敲除小鼠模型初步表型分析显示,Lep基因敲除纯合子小鼠表现出肥胖、高血糖、高胰岛素、脂质代谢紊乱、肝功能异常等表型;病理学检测显示,Lep基因敲除小鼠肝肿大,并出现肝细胞空泡化等脂肪变性现象.结论 成功构建Lep基因敲除小鼠模型,该模型或可用于肥胖和糖尿病发病机制及其药物研发.%Objective To provide mouse models for obesity and diabetes research and drug development,the Leptin (Lep) gene knockout mouse model was established and analyzed.Methods The Lep gene knockout mouse model was established by using embryonic stem cell and homologus recombination technology.Body weight and plasma glucose were measured,and the three genotypes of Lep gene knockout mice were sacrificed for detection of the serum biochemistry parameters.All the data generated from Lep gene knockout mice were compared with age-matched heterozygote(He) and wild type (WT) mice in statistics.Pathological changes of hepatic and kidney tissues between Lep gene knockout and WT mice were observed under microscope.Results The Lep gene knockout mouse model was established.Preliminarily phenotypic analysis show that Lep gene knockout mice develop obesity and hyperinsulinemia,hyperglycemia,lipid metabolism disorder,liver dysfunction.From the pathological analysis,the hepatocyte swelling and macro vacuolar steatosis were observed.Conclusion The Lep gene knockout mouse model was established and it could be used for obesity and diabetes research and drug development.