Nature 376, 167 - 170 (13 July 2002); doi:10.1038/376167a0

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

Amer A. Beg^*, William C. Sha^*, Roderick T. Bronson^†, Sankar Ghosh^‡ & David Baltimore^§

^*Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
^†Department of Pathology, Tufts University School of Medicine and Veterinary Medicine, Boston, Massachusetts 02111, USA
^‡Section of Immunobiology and the Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA

NF-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 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-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 IB 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-B-regulated pathways.

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