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.
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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).
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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
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DOI: https://doi.org/10.1038/376167a0
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