The two male gametes share equal ability to fertilize the egg cell in Arabidopsis thaliana

TNFα is a pleotropic cytokine that exerts its effect in many cell types via TNFR. In spite of their well-established roles in various biological events, neither TNFα nor TNFR is essential for normal mouse development, and mice deficient in either, like CARP2-null mice, developed normally and exhibited no defects without a challenge [6,7]. Similarly, deletion in mice of c-IAP or c-IAP2, proteins with a CARP-like carboxy-terminal RING domain and which play an important role in TNFR–RIP signaling, caused no overt phenotype. In contrast, mice deficient in other important regulators (e.g., RIP, A20, or TRAF2) had obvious defects, owing partly to their well-established additional roles in multiple signaling pathways. While knockout studies in mice remain the standard for gene-function analysis, it is important to keep in perspective their limitations in identifying the biological roles. For example, the loss of XIAP, an E3 implicated in receptor signaling, had no major effect in mice whereas in humans it caused X-linked lymphoproliferative syndrome [8,9]. Although in vitro studies using cell lines must be interpreted with caution, they do serve their objective, recent examples being the deciphering of autocrine TNF signaling caused by acute c-IAP deficiency that could not be inferred from characterization of the knockout mice [0]. We are inclined to believe that CARPs limit the intensity or duration of signaling during endocytosis in a cell-type-specific manner. It remains possible that in vivo CARP regulation of RIP may not primarily affect the activation of NF-κB, but rather other responses such as MAP kinase activation or necrosis, in which RIP is involved. Given that CARPs can also affect p53 and apical caspases [], an important role for these molecules in cell-death pathways cannot be ruled out. Further analysis of CARP/CARP2 knockout mice will increase our understanding of their physiological function(s).