Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1

Jianke Zhang, Dragana Cado, Ann Chen, Nisha H. Kabra and Astar Winoto ()
Additional contact information
Jianke Zhang: University of California at Berkeley
Dragana Cado: University of California at Berkeley
Ann Chen: University of California at Berkeley
Nisha H. Kabra: University of California at Berkeley
Astar Winoto: University of California at Berkeley

Nature, 1998, vol. 392, issue 6673, 296-300

Abstract: Abstract Programmed cell death, or apoptosis, is important in homeostasis of the immune system: for example, non-functional or auto-reactive lymphocytes are eliminated through apoptosis. One member of the tumour necrosis factor receptor (TNFR) family, Fas (also known as CD95 or Apo-1), can trigger cell death and is essential for lymphocyte homeostasis1,2. FADD/Mort1 (3–6) is a Fas-associated protein that is thought to mediate apoptosis by recruiting the protease caspase-8 (refs 7, 8). A dominant-negative mutant of FADD inhibits apoptosis initiated by Fas and other TNFR family members6,9,10,11,12,13,14. Other proteins, notably Daxx, also bind Fas and presumably mediate a FADD-independent apoptotic pathway15. Here we investigate the role of FADD in vivo by generating FADD-deficient mice. As homozygous mice die in utero, we generated FADD−/− embryonic stem cells and FADD−/− chimaeras in a background devoid of the recombination activating gene RAG-1, which activates rearrangement of the immunoglobulin and T-cell receptor genes. We found that thymocyte subpopulations were apparently normal in newborn chimaeras. Fas-induced apoptosis was completely blocked, indicating that there are no redundant Fas apoptotic pathways. As these mice age, their thymocytes decrease to an undetectable level, although peripheral T cells are present in all older FADD−/− chimaeras. Unexpectedly, activation-induced proliferation is impaired in these FADD−/− T cells, despite production of the cytokine interleukin (IL)-2. These results and the similarities between FADD−/− mice and mice lacking the β-subunit of the IL-2 receptor suggest that there is an unexpected connection between cell proliferation and apoptosis.

Date: 1998
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/32681 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:392:y:1998:i:6673:d:10.1038_32681

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/32681

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().