摘要
目的:建立BCR-ABL1^+粒细胞白血病小鼠模型,为研究白血病的发病机制和药物开发提供理想的平台.方法:利用含有p MSCV-BCR/ABL1-IRES-GFP逆转录病毒上清感染6~10周龄C57BL/6供者小鼠的骨髓细胞,移植给致死量射线照射的同种同型受者小鼠,建立BCR-ABL1^+粒细胞白血病小鼠模型;监测移植小鼠的体质量,生存率;流式细胞仪检测小鼠外周血有核细胞GFP表达(代表有核细胞表达BCR/ABL1)和细胞分型;观察小鼠脾脏、肺脏和肝脏等器官大体形态和HE染色变化.结果:移植20 d后,移植小鼠呈现弓背、活动性减少、精神萎靡的状态,体质量明显降低;流式细胞仪检测外周血中出现GFP^+细胞,并且随着移植时间的延长,GFP^+粒细胞明显增多.移植小鼠的生存率较对照组明显降低.移植小鼠发病后呈现脾脏显著增大、肺出血、肺脏及肝脏出现白色结节和HE染色呈现大量细胞浸润,且小鼠脾脏中有核细胞的80%为GFP^+Gr-1^+细胞,即BCR-ABL1^+粒细胞白血病细胞.结论:利用此方法成功建立了BCR-ABL1^+粒细胞白血病小鼠模型,为研究慢性粒细胞白血病机制和治疗提供了平台.
AIM:To establish the BCR-ABL1+myeloid leukemia model and provide a better platform for studying the mechanism of BCR-ABLV myeloid leukemia and the effect of therapeutic drugs in vivo.METHODS:The bone marrow cells from C57BL/6donor mouse treated by5-Fu were transfected with the pMSCVBCR/ABL1-IRES-GFP retroviral supernatant,then transplanted into irradiated C57BL/6recipient mice to establish the BCRABLVmyeloid leukemia mouse model.The weight loss,morbidity,volume of spleen and lung of transplantation mice were monitored daily for signs.The GFP expression(wihch represent BCR/ABL1expression)in the peripheral blood nucleated cells of the recipient mice and the cell classification were detected by flow cytometry.The spleen,lungs and other organs in general form and HE staining of mice were observed.RESULTS:The recipient mice obviously lost weight20days after transplantation.The GFP+leukemic cells are found in peripheral blood and the number of GFP+leukemic cells in peripheral blood increased with time.After transplantation,the survival rate of recipient mice was significantly lower than that of the control group.The recipient mice showed a significant increase in the spleen size,and the white nodules appeared on the lung and liver,the HE staining of lung and liver presented a large number of cell infiltrates,and the80%of nucleated cells in the mice spleen was the GFP+Gr-1+cells,namely the BCR-ABL1+granulocyte leukemia cells.CONCLUSION:We utilize this method to establish BCR-ABL1+myeloid leukemia mouse model successfully in order to provide a better platform for studying the mechanism of BCR-ABL1+myeloid leukemia and the effect of therapeutic drugs in vivo.
作者
张萍
李琛
郑铭喆
张华
季延红
ZHANG Ping;LI Chen;ZHENG Ming-Zhe;ZHANG Hua;JI Yan-Hong(Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China)
出处
《转化医学电子杂志》
2017年第10期31-34,共4页
E-Journal of Translational Medicine
基金
国家自然科学基金面上项目(31170821
31370874
81670157)
