三转基因银屑病小鼠模型建立与表型分析  

Establishment of the psoriasis transgenic mouse model and analysis of the phenotype

作　　者：高祥[1] 刘宁[1] 葛文萍[1] 潘烁[1] 张海涛[1] 张连峰[1] 董伟[1] 

机构地区：[1]北京协和医学院,中国医学科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,北京100021

出　　处：《中国比较医学杂志》2015年第7期11-15,I0001,共6页Chinese Journal of Comparative Medicine

基　　金：国家科技支撑计划课题“基因工程大鼠模型的研发与示范”(2014BAI02B01)

摘　　要：目的尿激酶型纤溶酶激活剂(PLAU)、尿激酶型纤溶酶激活剂受体(PLAUR)和信号传导与转录激活因子3(STAT3)是参与银屑病病理发生的重要基因。本文目的是制备皮肤特异性表达PLAU、PLAUR和STAT3三种基因的转基因小鼠,建立可进行性再现银屑病病理进程的小鼠模型。方法将PLAU、PLAUR和STAT3基因分别插入牛角蛋白5启动子(BK5)下游,构建转基因表达载体,通过显微注射法建立在皮肤组织同时高表达PLAU、PLAUR和STAT3三种基因的转基因C57BL/6J小鼠。利用PCR法鉴定转基因小鼠的基因型,Western blot检测基因表达水平,HE染色观察皮肤病理表型。结果 PLAU、PLAUR和STAT3三种基因在选定的转基因小鼠皮肤组织均有明显表达;转基因小鼠与同龄野生型小鼠相比表皮状态差,炎症明显;4月龄的转基因小鼠真皮变簿,表皮过度角化、棘层增厚,毛囊减少、发育异常、部分毛囊内未见毛干,角化不全区域内可见Munro氏小脓肿,真皮炎细胞浸润。结论建立了稳定传代的皮肤特异性表达PLAU、PLAUR和STAT3基因的转基因小鼠品系,转基因小鼠具有进行性的银屑病表型,可以作为多病因综合银屑病小鼠模型。Objective To develop a model that could copy the pathological development of psoriasis, the triple-transgenic mice that harboring Plasminogen activator, urokinase （ PLAU） ,PLAU receptor （ PLAUR） and signal transducer and activator of transcription 3 （ STAT3 ） were generated.They are the important genes involved in the pathological development of psoriasis.Methods The transgenic plasmid was constructed by insertion of the PLAU, PLAUR and STAT3 into the downstream bovine keratin 5 promoter respectively.The transgenic mouse was produced by microinjection and the genotyping was detected by PCR.The expression level of the transgenic gene was determined by Western blotting.The pathological changes were observed by HE staining.Results One mouse line was selected with over expression of the PLAU, PLAUR and STAT3 in the tissue of skin.The transgenic mice showed decreased dermal layer, a hyperkeratinized cuticular layer and increased stratum spinosum.The number of hair follicle was reduced and developed abnormally in the transgenic mice.The Munro abscess in the dermal layer and the increased inflammatory cell infiltrates in dermal layer were also observed in the transgenic mice.Conclusions A transgenic mouse line was produced and passage stably, which expressed the PLAU, PLAUR and STAT3 in the tissue of skin and developed the psoriasis progressively.All of our results suggested that the transgenic mice were a useful animal model for psoriasis.

关 键 词：银屑病 信号传导与转录激活因子3 尿激酶型纤溶酶激活剂 转基因小鼠 

分 类 号：R-332[医药卫生]