AIM: To explore the role of the adaptor molecule in liver regeneration after partial hepatectomy (PH).METHODS: We used transgenic mice expressing an N-terminal truncated form of MORT1/FADD under the control of the albumin promoter. As previously shown,this transgenic protein abrogated CD95- and CD120a-mediated apoptosis in the liver. Cyclin A expression was detected using Western blotting. ELISA and RT-PCR were used to detect IL-6 and IL-6 mRNA, respectively. DNA synthesis in liver tissue was measured by BrdU staining.RESULTS: Resection of 70% of the liver was followed by a reduced early regenerative response in the transgenic group at 36 h. Accordingly, 36 h after hepatectomy, cyclin A expression was only detectable in wild-type animals. Consequently, the onset of liver mass restoration was retarded as measured by MRI volumetry and mortality was significantly higher in the transgenic group.CONCLUSION: Our data demonstrate for the first time an involvement of the death receptor molecule MORT1/FADD in liver regeneration, beyond its well described role as part of the intracellular death signaling pathway.