Signals triggered by tumor necrosis factor (TNF) are mediated by its two receptors: the 55 kDa TNF receptor one (TNF-R1) and the 75 kDa TNF receptor two (TNF-R2). Activation of TNF-R1 induces cell death, NF-kappa B activation, inflammatory response and anti-viral activity, while TNF-R2 mainly stimulates cell proliferation and NF-kappa B activation. The TNF-R2-associated factor TRAF2 has been shown to mediate activation of NF-kappa B by TNF-R2 and CD40. The human TNF-R1-associated death domain protein (TRADD) induces cell death and NF-kappa B activation when overexpressed. Here we describe the cloning and gene structure of the mouse homolog of TRADD. Mouse TRADD shares 75% overall amino acid sequence identity with human TRADD, suggesting high conservation of function. Mouse TRADD specifically interacts with wild type TNF-R1 but not with a truncated mutant TNF-R1 lacking its C-terminal 20 amino acids. Like human TRADD, mouse TRADD also induces activation of NF-kappa B and cell death. The expression of TRADD in mouse embryo appears developmentally regulated. The mTRADD gene contains four exons, with the fourth exon encoding all of the death domain. The mouse TRADD gene was localized to the distal region of chromosome 8.