Exonuclease-1缺失延缓端粒酶缺失小鼠造血微环境的衰老

目的 研究Exo-1对端粒酶缺失小鼠造血微环境衰老的影响.方法 以端粒酶基因敲除小鼠( Terc-/-)和Exo-1基因敲除小鼠(Exo -1-/-)杂交,并进一步互交产生第三代端粒酶基因敲除小鼠(G3Terc -/-)以及第三代Terc和Exo-1双基因敲除小鼠(G3Terc-/- Exo-1-/-).以CD45.1野生型小鼠的骨髓细胞为供体,以2月龄G3Terc-/-或G3Terc-/- Exo-1-/-小鼠为受体,进行骨髓移植.在受体小鼠9月龄时,取骨髓、脾脏、胸腺、外周血等组织器官的细胞进行流式分析,研究G3 Terc-/-和G3Terc-/-Exo -1-/-受体小鼠中的野生型供体来源的造血干细胞的发育分化.结果 同G3Terc-/-小鼠相比,G3Terc-/- Exo-1-/-双基因敲除受体小鼠骨髓中野生型供体来源的B220+细胞比例升高,前体B细胞的比例也明显升高；脾脏B220+细胞的比例明显升高；胸腺发育正常；外周血中B220+细胞比例升高.结论 Exo-1缺失延缓了端粒酶基因敲除小鼠造血系统微环境的衰老,从而逆转了端粒功能障碍引起的骨髓造血干细胞发育分化异常.

Exonuclease-1 Deletion Rescues Hematopoietic Stem Cell Environmental Defect of Telomerase-deficient Mice

Objective To investigate the influence of Exo-1 gene deletion on the aging of the hematopoietic stem cell environmental defect of telomerase-deficient mice.Methods Recipients were the 3rd generation telomerase knockout mice(G3 Terc-/-) or the 3rd generation telomerase and Exo-1 gene double knockout mice(G3Terc-/-Exo-1-/-).Bone marrow cells were isolated from CD45.1 mice,and then injected into recipients at 2 month of age.Recipient mice were sacrificed at 9 month of age,the bone marrows,spleen,thymus and peripheral blood were collected and analyzed by flow cytometer.Results Percentage of B220+ cells increased in the wildtype donor derived bone marrow,spleen and peripheral blood cells in G3 Terc-/-Exo-1-/-double knockout recipient mice compared to those in G3Terc-/-recipient mice.Conclusion Exo-1 gene deletion rescued the hematopoietic stem cell environmental defect,and reversed the abnormal B cell development of hematopoietic stem cells.