Exo-1基因对端粒酶缺陷小鼠造血干细胞植入效率的影响  

Influence of Exo-1 gene on the chimerism rate in telomerase-defecient mice

作　　者：石桂英[1] 陈显达[1] 陈陟阳[1] 鞠振宇[1] 

机构地区：[1]中国医学科学院北京协和医学院实验动物研究所,北京100021

出　　处：《中国实验动物学报》2011年第2期95-99,186,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然基金面上项目[30771189];北京市科委科技新星计划[2008A115]

摘　　要：目的利用不同的造血干细胞移植方式,探讨Exo-1基因缺失对端粒酶基因敲除小鼠的造血干细胞植入效率的影响。方法以CD45.1小鼠的骨髓细胞或骨髓造血干细胞为供体,以端粒酶基因敲除小鼠或Exo-1基因和端粒酶基因双敲除小鼠为受体,在给予不同剂量X线照射或不照射的情况下,重复进行静脉注射全骨髓细胞或分选的骨髓造血干细胞(c-kit+、Sca-1+、lineage-,KSL),于移植后1个月取外周血,流式分析嵌合率。结果未经X线照射及1 Gy、2 Gy照射情况下,端粒酶基因缺陷受体小鼠的外周血中供体来源的细胞嵌合率较低;6 Gy照射后,供体来源的外周血细胞嵌合率仍低于50%,而且端粒酶基因缺陷受体小鼠在移植后1个月内死亡较多;3 Gy照射可形成较高嵌合率,Exo-1基因缺失对端粒酶缺陷小鼠的造血干细胞植入效率的影响不显著。结论以端粒酶缺陷小鼠作为衰老模型研究造血干细胞植入效率时,3 Gy X线照射能够有效地形成较高的外周血供体细胞的嵌合率,但是Exo-1基因没有进一步提高造血干细胞在端粒酶敲除小鼠的植入效率。Objective To investigate the influence of Exo-1 gene deletion on the engraftment of hematopoietic stem cell（HSC） transplantation by different methods into the telomerase knockout mice.Methods Bone marrow cells or KSL（（c-kit ^＋,Sca-1^ ＋,lineage^-） cells were isolated from CD45.1 mice,and then injected into recipients,which were telomer-ase gene knockout or Exo-1 and telomerase gene double knockout mice with or without irradiation.At 1 month later,pe-ripheral blood was collected and analyzed by flow cytometry.Results Low chimerisms of donor-derived cells were ob-served in recipients without irradiation or with 1 Gy,2 Gy irradiation.With 6 Gy irradiation,the chimerisms were below 50%,and died in 1 month.With 3 Gy irradiation,most mice lived with high chimerisms.Conclusions 3 Gy X-ray irra-diation gives rise to high chimerisms in telomerase knockout mice,whereas Exo-1 gene does not further increase the chimer-isms of HSC transplantation.

关 键 词：端粒酶基因缺陷 骨髓移植 造血干细胞 衰老 

分 类 号：Q95-33[生物学—动物学] R457.7[医药卫生—治疗学]