Beg A A, Sha W C, Bronson R T, Ghosh S, Baltimore D
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Nature. 1995 Jul 13;376(6536):167-70. doi: 10.1038/376167a0.
NF-kappa B, which consists of two polypeptides, p50 (M(r) 50K) and p65/RelA (M(r) 65K), is thought to be a key regulator of genes involved in responses to infection, inflammation and stress. Indeed, although developmentally normal, mice deficient in p50 display functional defects in immune responses. 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.
核因子-κB由两种多肽p50（分子量50K）和p65/RelA（分子量65K）组成，被认为是参与感染、炎症和应激反应的基因的关键调节因子。实际上，尽管发育正常，但p50基因缺失的小鼠在免疫反应中表现出功能缺陷。在此我们描述了核因子-κB的RelA亚基基因缺失小鼠的产生。RelA基因座的破坏导致妊娠15 - 16天时胚胎致死，同时肝脏因程序性细胞死亡或凋亡而大量退化。RelA基因缺失小鼠的胚胎成纤维细胞在肿瘤坏死因子（TNF）介导的IκBα和粒细胞/巨噬细胞集落刺激因子（GM-CSF）信使RNA诱导方面存在缺陷，尽管这些转录本的基础水平未改变。这些结果表明RelA在核因子-κB调节的途径中控制诱导性转录，但不控制基础转录。
