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.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Processing stimulus dynamics by the NF-κB network in single cells
Experimental & Molecular Medicine Open Access 01 December 2023
-
NF-κB subunits direct kinetically distinct transcriptional cascades in antigen receptor-activated B cells
Nature Immunology Open Access 31 July 2023
-
KappaBle fluorescent reporter mice enable low-background single-cell detection of NF-κB transcriptional activity in vivo
Mucosal Immunology Open Access 19 May 2022
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Baeuerle, P. A. & Henkel, T. A. Rev. Immun. 12, 141–179 (1994).
Sha, W. C., Liou, H.-C., Tuomanen, E. I. & Baltimore, D. Cell 80, 321–330 (1995).
Wyllie, A. H., Morris, R. G., Smith, A. L. & Dunlop, D. J. Path. 142, 67–77 (1994).
Gavrieli, Y., Sherman, Y. & Ben-Sasson, S. A. J. Cell Biol. 119, 493–501 (1992).
Grilli, M., Chiu, J.-S. & Lenardo, M. J. Int. Rev. Cytol. 143, 1–63 (1991).
Haskill, S. et al. Cell 65, 1281–1289 (1991).
Thompson, J. E., Phillips, R. J., Erdjument-Bromage, H., Tempst, P. & Ghosh, S. Cell 80, 573–582 (1995).
Beg, A. A. & Baldwin, A. S. Genes Dev. 7, 2064–2070 (1993).
Scott, M. L., Fujita, T., Liou, H.-C., Nolan, G. P. & Baltimore, D. Genes Dev. 7, 1266–1276 (1993).
Rice, N. R., MacKichan, M. L. & Israel, A. Cell 71, 243–253 (1992).
Burkly, L. et al. Nature 373, 531–536 (1995).
Weih, F. et al. Cell 80, 331–340 (1994).
Abbadie, C. et al. Cell 75, 889–912 (1993).
Thanos, D. & Maniatis, T. Cell 80, 529–532 (1995).
Stein, B. et al. EMBO J. 10, 3879–3891 (1993).
Hilberg, F., Aguzzi, A., Howells, N. & Wagner, E. F. Nature 365, 179–181 (1993).
Cressman, D. E., Greenbaum, L. E., Haber, B. A. & Taub, R. J. biol. Chem. 269, 30429–30435 (1994).
Beg, A. A., Finco, T. S., Nantermet, P. V. & Baldwin, A. S. Molec. cell. Biol. 13, 3301–3310 (1993).
Tybulewicz, V. L. J., Crawford, C. E., Jackson, P. K., Bronson, R. T. & Mulligan, R. C. Cell 65, 1153–1163 (1991).
Nolan, G. P., Ghosh, S., Liou, H.-C., Tempst, P. & Baltimore, D. Cell 64, 961–969 (1991).
Plump, A. S. et al. Cell 71, 343–353 (1992).
Liou, H.-C., Sha, W. C., Scott, M. L. & Baltimore, D. Molec. cell. Biol. 14, 5349–5359 (1994).
Montgomery, R. A. & Dallman, M. J. J. Immun. 147, 554–560 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Beg, A., Sha, W., Bronson, R. et al. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB. Nature 376, 167–170 (1995). https://doi.org/10.1038/376167a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/376167a0
This article is cited by
-
Processing stimulus dynamics by the NF-κB network in single cells
Experimental & Molecular Medicine (2023)
-
Excitation–transcription coupling, neuronal gene expression and synaptic plasticity
Nature Reviews Neuroscience (2023)
-
NF-κB subunits direct kinetically distinct transcriptional cascades in antigen receptor-activated B cells
Nature Immunology (2023)
-
KappaBle fluorescent reporter mice enable low-background single-cell detection of NF-κB transcriptional activity in vivo
Mucosal Immunology (2022)
-
TNF in the liver: targeting a central player in inflammation
Seminars in Immunopathology (2022)