敲除ADAR1抑制Notch1诱导小鼠T淋巴细胞白血病的发生

ADAR1 Knockout Inhibits Notch1-induced T-ALL in Mice

目的:探索ADAR1对于小鼠急性T淋巴细胞白血病(T cell acute lymphoblastic leukemia,T-ALL)发生发展的影响。方法:通过杂交繁殖获得Lck-Cre;ADAR1^(lox/lox)小鼠及对照组ADAR1^(lox/lox)小鼠;采用免疫磁珠法富集两组小鼠的lin-细胞,用携带MSCV-ICN1-IRES-GFP质粒的逆转录病毒分别感染上述lin-细胞,流式细胞术检测感染效率,分选并移植相同数量的GFP+细胞至受体小鼠中。在移植后持续观察并统计两组小鼠生存情况。结果:成功获得了T细胞特异敲除ADAR1的小鼠,并成功建立了Notch1诱导的小鼠T-ALL白血病模型。对照组小鼠在移植后发病,符合T-ALL特征;相反,ADAR1敲除组小鼠没有发生白血病。结论:ADAR1在Notch1诱导的T-ALL白血病的发生过程中起关键作用。

Objective: To investigate the effect of ADAR1 on the occurrence and development of mouse T cell acute lymphoblastic leukemia（ T-ALL）. Methods: Lck-Cre; ADAR1lox/loxmice w ere generated through interbreeding. The lineage-cells of Lck-Cre; ADAR1lox/loxmice and the control w ere enriched respectively by the means of M ACS,and the lincells w ere transfected w ith retrovirus carrying M SCV-ICN1-IRES-GFP fusion gene. Then the transfection efficiency w as detected by the means of FACS,and the same number of GFP+cells w ere transplanted into lethally irradiated recipient mice to observe the survival of mice in 2 recipient group after transplantation. Results: T cell- specific knockout ADAR1 mice w ere generated, and Notch1-induced T-ALL mouse model w as established successfully. The leukemia w ith T-ALL characteristics occured in the mice of control group,but did not in the ADAR1 kmockout mice after transplantation.Conclusions: ADAR1 plays a key role in the incidence and development of Notch1-induced T-ALL.