EMBRYONIC LETHALITY AND LIVER DEGENERATION IN MICE LACKING THE RELA COMPONENT OF NF-KAPPA-B
EMBRYONIC LETHALITY AND LIVER DEGENERATION IN MICE LACKING THE RELA COMPONENT OF NF-KAPPA-B
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DOI：
10.1038/376167a0
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发表时间：
1995-07-13
期刊：
影响因子：
64.8
通讯作者：
BALTIMORE, D
中科院分区：
文献类型：
--
作者：
BEG, AA;SHA, WC;BALTIMORE, D
NF-κ B由两种多肽p50（M，50 K）和p65/RelA（M（r）65 K）组成，被认为是参与对感染、炎症和应激反应的基因的关键调节因子（1）。事实上，尽管发育正常，但p50缺陷的小鼠在免疫应答中显示出功能缺陷（2）。在此，我们描述了NF-κ B B的RelA亚基缺陷小鼠的产生。relA基因座的破坏导致妊娠15-16天的胚胎死亡，伴随着通过程序性细胞死亡或细胞凋亡引起的肝脏大规模变性。来自RelA缺陷小鼠的胚胎成纤维细胞在肿瘤坏死因子（TNF）介导的I κ B α和粒细胞/巨噬细胞集落刺激因子（GM-CSF）的信使RNA诱导中有缺陷，尽管这些转录物的基础水平未改变。这些结果表明RelA控制NF-κ B调节途径中的诱导型转录，但不控制基础转录。
NF-kappa B, which consists of two polypeptides, p50 (M, 50K) and p65/RelA (M(r) 65K), is thought to be a key regulator of genes involved in responses to infection, inflammation and stress(1). Indeed, although developmentally normal, mice deficient in p50 display functional defects in immune responses(2). Here we describe the generation of mice deficient in the RelA subunit of NF-kappa B. Disruption of the relA locus leads to embryonic lethality at 15-16 days of gestation, concomitant with a massive degeneration of the liver by programmed cell death or apoptosis. Embryonic fibroblasts from RelA-deficient mice are defective in the tumour necrosis factor (TNF)-mediated induction of messenger RNAs for I kappa B alpha and granulocyte/macrophage colony stimulating factor (GM-CSF), although basal levels of these transcripts are unaltered. These results indicate that RelA controls inducible, but not basal, transcription in NF-kappa B-regulated pathways.