Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB
Abstract
NF-κB, 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-κB. 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 IκBα 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-κB-regulated pathways.
Additional Information
© 1995 Nature Publishing Group. Received 12 April 1995; Accepted 16 May 1995; Issue Date 13 July 1995. We thank the knockout facility at the Rockefeller University for help in generation of chimaeric mice, and A. Gifford for help in genotyping. We also thank K. Macleod, T. Jacks and members of the Baltimore laboratory for discussion. A.A.B. is supported by a postdoctoral grant from the Cancer Research Institute. W.C.S. is supported by a fellowship from the NIH. This work was supported by the NIH and by the Amgen Corporation.Additional details
- Eprint ID
- 103133
- Resolver ID
- CaltechAUTHORS:20200512-101348818
- Cancer Research Institute
- NIH
- Amgen
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2020-05-12Created from EPrint's datestamp field
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2021-11-16Created from EPrint's last_modified field