人载脂蛋白A1基因转基因小鼠的建立  

Establishment of a human APOA1 transgenic mouse model

作　　者：张旭[1] 高昆[1] 张海涛[1] 高翔[1] 葛文平[1] 张小娟[1] 张连峰[1] 董伟[1] 

机构地区：[1]中国医学科学院,北京协和医学院,医学实验动物研究所,卫生部人类疾病比较医学重点实验室,国家中医药管理局人类疾病动物模型三级实验室,北京10002

出　　处：《中国实验动物学报》2011年第6期461-464,共4页Acta Laboratorium Animalis Scientia Sinica

基　　金：卫生部:实验动物和人类疾病动物模型资源扩展(200802036)

摘　　要：目的建立系统性表达人载脂蛋白A1(APOA1)基因的转基因小鼠。方法 将人APOA1基因插入系统性表达启动子下游,构建转基因表达载体,通过显微注射法建立人APOA1转基因C57BL/6J小鼠。并利用特异引物PCR法鉴定转基因小鼠的基因型,Western blot检测基因表达水平,血生化分析检测不同月龄转基因小鼠与同龄野生型小鼠的血脂指标。结果建立了2个不同表达水平的人APOA1基因的转基因小鼠品系;转入的人APOA1基因在血液、肝脏、心脏、肾脏、脾脏、血管组织中均有明显表达;血生化分析结果显示不同月龄转基因小鼠的血浆高密度脂蛋白胆固醇水平高于同龄的野生型小鼠,甘油三酯水平低于同龄野生型小鼠。结论成功建立了系统性表达人APOA1基因的转基因小鼠,为研究高血脂以及高血脂相关的心血管病提供了工具。Objective To establish a human APOA1 transgenic mouse model.Methods The transgenic plasmid was constructed by inserting human APOA1 gene into the downstream of the human ubiquitin C（Ubc） promoter.The transgenic mice were produced by microinjection and the genotyping was detected by PCR.The expression level of the gene was determined by Western blotting.The levels of blood lipids of the mice of different ages were detected using a biochemical analyzer.Results Two human APOA1 gene transgenic mouse lines with different expression levels were established.The expression levels of human APOA1 gene in blood,liver,heart,kidney,spleen and blood vessels of the transgenic mice were significantly higher than those from wild type mice.The blood biochemical assay showed that the level of HDL-cholesterol in the transgenic mice was significantly higher and the level of TG was lower than that of the wild type mice.Conclusions The transgenic mice with overexpression of human APOA1 gene have been successfully established.It may be a useful animal model for further research of hyperlipidemia and related angiocardiopathy.

关 键 词：载脂蛋白A1 转基因小鼠 高密度脂蛋白胆固醇 

分 类 号：Q95-33[生物学—动物学]