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.%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 (GBTerc-/- 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.
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