Dominant interfering fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome

@article{Fisher1995DominantIF,
  title={Dominant interfering fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome},
  author={Galen H Fisher and Fredric J Rosenberg and Stephen E. Straus and Janet K. Dale and Lindsay A. Middelton and Albert Y Lin and Warren Strober and Michael J. Lenardo and Jennifer M. Puck},
  journal={Cell},
  year={1995},
  volume={81},
  pages={935-946}
}

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References

SHOWING 1-10 OF 69 REFERENCES
A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease.
TLDR
The clinical and immunological features of this syndrome resemble the lymphoproliferative/autoimmune disease seen in lpr and gld mice, and could be augmented by co-stimulation with an antibody directed at the CD28 determinant.
Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis
TLDR
The Ipr mice develop lymphadenopathy and suffer from a systemic lupus erythematosus-like autoimmune disease, indicating an important role for Fas antigen in the negative selection of autoreactive T cells in the thymus.
A specific intercellular pathway of apoptotic cell death is defective in the mature peripheral T cells of autoimmune lpr and gld mice
TLDR
Data reported here indicate that the Fas receptor and its ligand, the wild‐type form of the gld gene product, are essential for antigen‐stimulated peripheral T cell apoptosis and support the importance of apoptotic regulation of lymphocyte persistence after antigen encounter in vivo.
Autoimmunity in mice bearing lprcg: a novel mutant gene.
A novel mutation at the lpr (lymphoproliferation)(Fas) locus, lprcg, that can complement gld (generalized lymphoproliferative disease) in induction of lymphadenopathy was discovered in CBA/K1Jms
Mature T cells of autoimmune lpr/lpr mice have a defect in antigen-stimulated suicide.
TLDR
It is shown that Mutant lpr/lpr mice exhibit an autoimmune syndrome similar to systemic lupus erythematosus and a defect in antigen-stimulated suicide of activated T cells in mature CD4+ and CD8+ T cell compartments, suggesting that antigen- Stimulated death of mature cells may be important both in establishing peripheral tolerance and in limiting inflammation during normal immune responses.
Female germ line mosaicism as the origin of a unique IL-2 receptor gamma-chain mutation causing X-linked severe combined immunodeficiency.
TLDR
Female germ line mosaicism is unusual, but its presence in this X-linked SCID family emphasizes the limitations of genetic diagnosis by linkage as compared with direct mutation analysis.
Mutations in the Fas antigen gene in lpr mice.
  • S. Nagata
  • Biology, Medicine
    Seminars in immunology
  • 1994
TLDR
The Fas antigen is a cell surface protein belonging to the tumor necrosis factor/nerve growth factor receptor family and it mediates apoptosis and a point mutation in the signal transducing domain of the cytoplasmic region abolishes the function of the Fas antigen.
Murine models of systemic lupus erythematosus.
...
1
2
3
4
5
...