Conditional deletion of the Bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly.
Conditional deletion of the Bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly.
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发表时间：
2000-11
期刊：
影响因子：
4.6
通讯作者：
K. Wagner;E. Claudio;E. Rucker;G. Riedlinger;C. Broussard;P. Schwartzberg;U. Siebenlist;L. Hennighausen
中科院分区：
文献类型：
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作者：
K. Wagner;E. Claudio;E. Rucker;G. Riedlinger;C. Broussard;P. Schwartzberg;U. Siebenlist;L. Hennighausen
Bcl-x是Bcl2家族的一员，已被认为对包括红系谱系在内的各种细胞类型的存活和成熟起重要作用。为了确定红细胞和其他成年组织中Bcl-x缺失的后果，我们使用Cre-loxP重组系统产生了Bcl-x基因条件缺陷的小鼠。在MMTV-LTR的控制下，通过表达Cre重组酶基因，实现了Bcl-x基因座的时空切除。在5周龄时，Bcl-x条件突变小鼠表现出巨核细胞过度增殖和循环血小板数量下降。三个月大的动物患有严重的溶血性贫血，未成熟红细胞增生和脾脏肿大。我们证明Bcl-x仅对成熟末期的红系细胞存活是必需的，其中包括循环中的去核网状细胞。脾和骨髓中未成熟红细胞的广泛增殖可能是由于组织缺氧导致晚期红细胞前体快速周转和红细胞生成加速的结果。在Bcl-x和Bax的条件双突变小鼠中证实，晚期红细胞死亡的增加与促凋亡因子Bax无关。条件缺乏Bcl-x的小鼠使我们首次研究了生理条件下Bcl-x缺乏对成年动物细胞增殖、成熟和存活的影响。
Bcl-x is a member of the Bcl2 family and has been suggested to be important for the survival and maturation of various cell types including the erythroid lineage. To define the consequences of Bcl-x loss in erythroid cells and other adult tissues, we have generated mice conditionally deficient in the Bcl-x gene using the Cre-loxP recombination system. The temporal and spatial excision of the floxed Bcl-x locus was achieved by expressing the Cre recombinase gene under control of the MMTV-LTR. By the age of five weeks, Bcl-x conditional mutant mice exhibited hyperproliferation of megakaryocytes and a decline in the number of circulating platelets. Three-month-old animals suffered from severe hemolytic anemia, hyperplasia of immature erythroid cells and profound enlargement of the spleen. We demonstrate that Bcl-x is only required for the survival of erythroid cells at the end of maturation, which includes enucleated reticulocytes in circulation. The extensive proliferation of immature erythroid cells in the spleen and bone marrow might be the result of a fast turnover of late red blood cell precursors and accelerated erythropoiesis in response to tissue hypoxia. The increase in cell death of late erythroid cells is independent from the proapoptotic factor Bax, as demonstrated in conditional double mutant mice for Bcl-x and Bax. Mice conditionally deficient in Bcl-x permitted us for the first time to study the effects of Bcl-x deficiency on cell proliferation, maturation and survival under physiological conditions in an adult animal.