Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic lethality

TS Doi, MW Marino, T Takahashi… - Proceedings of the …, 1999 - National Acad Sciences
TS Doi, MW Marino, T Takahashi, T Yoshida, T Sakakura, LJ Old, Y Obata
Proceedings of the National Academy of Sciences, 1999National Acad Sciences
Mice lacking the RelA (p65) subunit of NF-κB die between days 14 and 15 of embryogenesis
because of massive liver destruction. Fibroblasts and macrophages isolated from relA−/−
embryos were found to be highly sensitive to tumor necrosis factor (TNF) cytotoxicity, raising
the possibility that endogenous TNF is the cause of liver cell apoptosis. To test this idea, we
generated mice lacking both TNF and RelA. Embryogenesis proceeds normally in such
mice, and TNF/RelA double-deficient mice are viable and have normal livers. Thus, the RelA …
Mice lacking the RelA (p65) subunit of NF-κB die between days 14 and 15 of embryogenesis because of massive liver destruction. Fibroblasts and macrophages isolated from relA−/− embryos were found to be highly sensitive to tumor necrosis factor (TNF) cytotoxicity, raising the possibility that endogenous TNF is the cause of liver cell apoptosis. To test this idea, we generated mice lacking both TNF and RelA. Embryogenesis proceeds normally in such mice, and TNF/RelA double-deficient mice are viable and have normal livers. Thus, the RelA-mediated antiapoptotic signal that protects normal cells from TNF injury in vitro can be shown to be operative in vivo.
National Acad Sciences