Alb-cre/DTR小鼠可诱导性肝损伤模型的建立

[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，可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0.625ng/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 Alb-cre和DTR小鼠杂交是繁育Alb-cre/DTR小鼠的较好方法，且PCR方法能够鉴定该小鼠，并能建立特异性肝损小鼠模型。

Establishment of an Alb-cre/DTR mouse model of inducible liver injury

Objective To analyze the Alb-cre/DTR mouse phenotype, and establish a model of induced liver damage to serve 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 tissue of the mice for genotying by PCR. Diphtheria toxin was intraperitoneally(i.p.)injected into the Alb-cre/DTR mice, then the body weights 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. The intraperitoneal injection of diphtheria toxin in a dose of 0.625 ng/g body weight significantly induced liver injury in these mice, as showed by the elevated levels of ALT and AST, the gross appearance of liver damage and the pathological changes such as necrosis in the liver tissue. Conclusions We have obtained a novel mouse strain of Alb-cre/DTR by crossing Alb-cre and DTR mice. Liver damages in those Alb-cre/DTR mice can be induced by injection of diphtheria toxin. This established mouse model of inducible liver damage is a useful platform for the studies of liver damage and recovery, as well as liver transplantation.