Chao D T, Linette G P, Boise L H, White L S, Thompson C B, Korsmeyer S J
Howard Hughes Medical Institute, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Exp Med. 1995 Sep 1;182(3):821-8. doi: 10.1084/jem.182.3.821.
The effect of Bcl-xL upon the developmental death of T cells was assessed by generating transgenic mice that expressed Bcl-xL within all thymocyte subsets. Bcl-xL protected thymocytes from a variety of apoptotic stimuli, including gamma irradiation, glucocorticoids, and anti-CD3 treatment. Bcl-xL altered thymocyte maturation, resulting in increased numbers of CD3int/hi and CD4-8+ thymocytes. Overall, the phenotype of Bcl-xL transgenics was essentially indistinguishable from a Bcl-2 transgenic model. Overexpression of Bcl-xL or Bcl-2 resulted in the down-regulation of the other molecule, providing further evidence of their reciprocal regulation. In a genetic test of redundancy, the Bcl-xL transgene rescued mature T cells in Bcl-2 null mice. Immunoprecipitation indicated that Bcl-xL, like Bcl-2, heterodimerized with the death-promoting molecule Bax in thymocytes. This in vivo model argues that Bcl-xL, like Bcl-2, functions in a common pathway to repress cell death.
通过构建在所有胸腺细胞亚群中表达Bcl-xL的转基因小鼠，评估了Bcl-xL对T细胞发育性死亡的影响。Bcl-xL保护胸腺细胞免受多种凋亡刺激，包括γ射线照射、糖皮质激素和抗CD3处理。Bcl-xL改变了胸腺细胞的成熟过程，导致CD3int/hi和CD4-8+胸腺细胞数量增加。总体而言，Bcl-xL转基因小鼠的表型与Bcl-2转基因模型基本无法区分。Bcl-xL或Bcl-2的过表达导致另一种分子的下调，进一步证明了它们的相互调节。在一项冗余性基因测试中，Bcl-xL转基因挽救了Bcl-2基因敲除小鼠中的成熟T细胞。免疫沉淀表明，Bcl-xL与Bcl-2一样，在胸腺细胞中与促死亡分子Bax形成异二聚体。这个体内模型表明，Bcl-xL与Bcl-2一样，在共同的途径中发挥作用以抑制细胞死亡。
