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

Mice lacking the RelA (p65) subunit of NF-KB die between days 14 and 15 of embryogenesis because of massive liver destruction. Fibroblasts and macroph ages isolated from reLA-/- embryos were found to be highly sensitive to tum or necrosis factor (TNF) cytotoxicity, raising the possibility that endogen ous TSF is the cause of liver cell apoptosis, To test this idea, we generat ed mice lacking both TNF and RelA Embryogenesis proceeds normally in such m ice, and TNF/RelA double-deficient mice are viable and have normal livers. Thus, the Rel-mediated antiapoptotic signal that protects normal cells from TNF injury in vitro can be shown to be operative in vivo.