Ex vivo whole-embryo culture of caspase-8-deficient embryos normalize their aberrant phenotypes in the developing neural tube and heart
Ex vivo whole-embryo culture of caspase-8-deficient embryos normalize their aberrant phenotypes in the developing neural tube and heart
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DOI：
10.1038/sj.cdd.4401090
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发表时间：
2002-11-01
影响因子：
12.4
通讯作者：
Yonehara, S
中科院分区：
文献类型：
--
作者：
Sakamaki, K;Inoue, T;Yonehara, S
caspase -8在caspase级联反应中起启动剂作用，是死亡受体诱导的凋亡通路中的关键分子。为了研究caspase-8在体内的生理作用，我们用基因靶向的方法培养了caspase-8缺陷小鼠。纯合子突变胚胎的第一个异常迹象是在胚胎外组织卵黄囊中观察到的。到胚胎日(E) 10.5，卵黄囊血管系统开始不正常地形成，随后突变胚胎在发育中的心脏和神经管中显示出各种缺陷。结果，所有突变胚胎在E11.5时死亡。重要的是，在E10.5-E11.5期间，纯合子突变的神经和心脏缺陷通过体外全胚胎培养得以修复，这表明这些缺陷很可能是继发于缺乏生理caspase-8活性。综上所述，这些结果表明caspase-8对胚胎发育是不可或缺的。
Caspase-8 plays the role of initiator in the caspase cascade and is a key molecule in death receptor-induced apoptotic pathways. To investigate the physiological roles of caspase-8 in vivo, we have generated caspase-8-deficient mice by gene targeting. The first signs of abnormality in homozygous mutant embryos were observed in extraembryonic tissue, the yolk sac. By embryonic day (E) 10.5, the yolk sac vasculature had begun to form inappropriately, and subsequently the mutant embryos displayed a variety of defects in the developing heart and neural tube. As a result, all mutant embryos died at E11.5. Importantly, homozygous mutant neural and heart defects were rescued by ex vivo whole-embryo culture during E10.5-E11.5, suggesting that these defects are most likely secondary to a lack of physiological caspase-8 activity. Taken together, these results suggest that caspase-8 is indispensable for embryonic development.