TARGETED DISRUPTION OF TRAF3 LEADS TO POSTNATAL LETHALITY AND DEFECTIVE T-DEPENDENT IMMUNE-RESPONSES

TRAF3 was found as a protein that binds to the cytoplasmic tail of CD4 0 but is part of a family of proteins with common structure and activi ty. To clarify the physiological roles of TRAF3, we introduced a TRAF3 null mutation in mice through homologous recombination. TRAF3-deficie nt mice appear normal at birth but become progressively runted, correl ating with progressive hypoglycemia and depletion of peripheral white cells. The mutant mice die by 10 days of age. Fetal liver cells from T RAF3-deficient embryos can reconstitute all hematopoietic lineages in lethally irradiated mice. However, these reconstituted mice are impair ed in their immune responses to T-dependent antigen, and their T cells are functionally defective. These findings indicate that TRAF3 is req uired for postnatal development and for a competent immune system.