T cell-specific FADD-deficient mice: FADD is required for early T cell development.
FADD/Mort1, initially identified as a Fas-associated death-domain containing protein, functions as an adapter molecule in apoptosis initiated by Fas, tumor necrosis factor receptor-I, DR3, and TRAIL-receptors. However, FADD likely participates in additional signaling cascades. FADD-null mutations in mice are embryonic-lethal, and analysis of FADD(-)/- T cells from RAG-1(-)/- reconstituted chimeras has suggested a role for FADD in proliferation of mature T cells. Here, we report the generation of T cell-specific FADD-deficient mice via a conditional genomic rescue approach. We find that FADD-deficiency leads to inhibition of T cell development at the CD4(-)CD8(-) stage and a reduction in the number of mature T cells. The FADD mutation does not affect apoptosis or the proximal signaling events of the pre-T cell receptor; introduction of a T cell receptor transgene fails to rescue the mutant phenotype. These data suggest that FADD, through either a death-domain containing receptor or a novel receptor-independent mechanism, is required for the proliferative phase of early T cell development.
Kabra
N H
NH
Cancer Research Laboratory and Division of Immunology, Department of Molecular and Cell Biology, 465 Life Science Addition, University of California, Berkeley, CA 94720-3200, USA.
Kang
C
C
Hsing
L C
LC
Zhang
J
J
Winoto
A
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D053200:Fas-Associated Death Domain Protein; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000166:cytology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein