Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB

AA Beg, WC Sha, RT Bronson, S Ghosh, D Baltimore - Nature, 1995 - nature.com
AA Beg, WC Sha, RT Bronson, S Ghosh, D Baltimore
Nature, 1995nature.com
NF-κB, which consists of two polypeptides, p50 (Mr 50K) and p65/RelA (Mr 65K), is thought
to be a key regulator of genes involved in responses to infection, inflammation and stress1.
Indeed, although developmentally normal, mice deficient in p50 display functional defects in
immune responses2. Here we describe the generation of mice deficient in the RelA subunit
of NF-κB. Disruption of the rel A locus leads to embryonic lethality at 15–16 days of
gestation, concomitant with a massive degeneration of the liver by programmed cell death or …
Abstract
NF-κB, which consists of two polypeptides, p50 (Mr 50K) and p65/RelA (Mr 65K), is thought to be a key regulator of genes involved in responses to infection, inflammation and stress1. Indeed, although developmentally normal, mice deficient in p50 display functional defects in immune responses2. 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.
nature.com