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Generation and Characterization of Smac/DIABLO-Deficient Mice

机译:Smac / DIABLO缺陷小鼠的产生和表征

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The mitochondrial proapoptotic protein Smac/DIABLO has recently been shown to potentiate apoptosis by counteracting the antiapoptotic function of the inhibitor of apoptosis proteins (IAPs). In response to apoptotic stimuli, Smac is released into the cytosol and promotes caspase activation by binding to IAPs, thereby blocking their function. These observations have suggested that Smac is a new regulator of apoptosis. To better understand the physiological function of Smac in normal cells, we generated Smac-deficient (Smac?/?) mice by using homologous recombination in embryonic stem (ES) cells. Smac?/? mice were viable, grew, and matured normally and did not show any histological abnormalities. Although the cleavage in vitro of procaspase-3 was inhibited in lysates of Smac?/? cells, all types of cultured Smac?/? cells tested responded normally to all apoptotic stimuli applied. There were also no detectable differences in Fas-mediated apoptosis in the liver in vivo. Our data strongly suggest the existence of a redundant molecule or molecules capable of compensating for a loss of Smac function.
机译:最近显示,线粒体促凋亡蛋白Smac / DIABLO通过抵消凋亡蛋白抑制剂(IAP)的抗凋亡功能来增强凋亡。响应凋亡刺激,Smac被释放到细胞质中,并通过与IAP结合而促进caspase活化,从而阻断其功能。这些观察结果表明,Smac是凋亡的新调节剂。为了更好地了解 Smac 在正常细胞中的生理功能,我们通过在小鼠体内进行同源重组,生成了Smac缺陷型( Smac ?/? )小鼠。胚胎干(ES)细胞。 Smac ?/? 小鼠可正常存活,生长和成熟,并且未显示任何组织学异常。尽管procaspase-3的体外裂解在 Smac ?/? 细胞的裂解物中受到抑制,但所有类型的培养的 Smac ?/? 细胞对所有施加的凋亡刺激均正常反应。体内肝脏中Fas介导的凋亡也没有可检测的差异。我们的数据强烈暗示存在一个或多个能够补偿Smac功能丧失的分子。

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