alb-credtr小鼠可you导性肝脏损伤模型的建立.docVIP

Alb-cre/DTR小鼠可诱导性肝脏损伤模型的建立 任晓楠，任蓉蓉，刘雪，杨华，秦波音，周晓辉 （上海市公共卫生临床中心，上海 201508） [摘要]目的建立Alb-cre/DTR双转基因小鼠模型并进行相关表型分析，在此基础上建立可诱导性肝损模型，用于肝脏疾病的相关研究。方法将引进的Alb-cre和DTR小鼠扩繁后，通过杂交的方式获得双转基因小鼠。提取小鼠尾部组织DNA，利用PCR方法进行基因型鉴定。在双转基因小鼠上腹腔注射白喉毒素，之后在不同时间点进行称重、采血，检测血清ALT、AST水平。结果将Alb-cre和DTR小鼠杂交、筛选后获得了Alb-cre/DTR双转基因小鼠，对该小鼠使用0.625 ng/g剂量的白喉毒素，可使小鼠血清中ALT与AST水平显著升高，解剖小鼠后观察到肝脏整体变白，HE染色结果显示肝细胞明显坏死。结论成功建立可诱导特异性肝损小鼠模型。 [关键词] Alb-cre；DTR；转基因；特异性肝损 [中图分类号] Q95-33 [文献标识码]A [文章编号] Establishment of Alb-cre/DTR mouse model forinducible liver injury REN Xiao-nan, REN Rong-rong, LIU Xue,YANG Hua, QIN Bo-yin, ZHOU Xiao-hui (Shanghai Public Health Clinical Center, shanghai 201508, China) [[Abstract]ObjectiveTo analysis Alb-cre/DTR mouse phenotype, establish induced a liver damage model for the basic researches of liver diseases. Methods The introduced Alb-cre and DTR mice were crossed to obtain Alb-cre/DTR mice and the genomic DNAs were extracted from the tail of the mice for genotying by PCR. Intraperitoneal（i.p.）injection of diphtheria toxin into the Alb-cre/DTR mouse, then the bodyweights were monitored and the sera were collected for the detection of serum ALT and AST levels. Results By crossing Alb-cre and DTR mice we obtained the Alb-cre and DTR double transgenic mouse. Intraperitoneal injection of 0.625 ng/g bodyweight diphtheria toxin can significantly induce the liver injury in these mice, as showed by the data of elevated levels of ALT and AST, the gross appearancesof liver damage by anatomy photosand the main pathological change in the liver tissue was necrosis. Conclusions We have obtained a novel mouse strain of Alb-cre/DTR by crossing Alb-cre and DTR mice. Those Alb-cre/DTR mice can be induced to shown liver injury sign by injection of diphtheria toxin. This established inducible liver damage mouse model is useful platform for the studies of liver damage and recovery, as well as liver transplantation. [Key words] Alb-cre; DTR; transgene;; induced liver injury 肝脏疾病是对人类威胁最大的疾病之一[1-2]，除病毒性肝炎外