T cell-specific FADD-deficient mice: FADD is required for early T cell development
| Autor: | Jianke Zhang, Lianne C. Hsing, Nisha H. Kabra, Chulho Kang, Astar Winoto |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cell division
T cell Transgene Fas-Associated Death Domain Protein T-Lymphocytes Mice Transgenic urologic and male genital diseases Mice medicine Cytotoxic T cell Animals FADD Receptor Adaptor Proteins Signal Transducing Mice Knockout Multidisciplinary biology T-cell receptor Biological Sciences Molecular biology Cell biology Mice Inbred C57BL medicine.anatomical_structure Death-inducing signaling complex biology.protein Mice Inbred CBA biological phenomena cell phenomena and immunity Carrier Proteins Cell Division |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 98(11) |
| ISSN: | 0027-8424 |
| Popis: | 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 ofFADD−/−T cells fromRAG-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. |
| Databáze: | OpenAIRE |
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