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      Targeted mutation in the Fas gene causes hyperplasia in peripheral lymphoid organs and liver.

      Nature genetics

      Animals, Antigens, CD95, genetics, Apoptosis, Base Sequence, Embryo, Mammalian, cytology, Gene Expression Regulation, Gene Targeting, Hyperplasia, Liver, pathology, Lymph Nodes, Mice, Mice, Inbred BALB C, Mice, Transgenic, Molecular Sequence Data, Mutation, Spleen, Stem Cells

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          Abstract

          Fas, a type I membrane protein that transduces an apoptotic signal, is expressed in lymphocytes as well as in various tissues such as the liver, lung and heart. The mouse lymphoproliferation (lpr) mutation is a leaky mutation in Fas. By means of gene targeting, we generated a mouse strain which is completely deficient in Fas. In addition to the massive production of lymphocytes, the Fas-null mice showed substantial liver hyperplasia, which was accompanied by the enlargement of nuclei in hepatocytes. The Fas system seems to play a role in the apoptotic process to maintain homeostasis of the liver as well as the peripheral lymphoid organs.

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          Most cited references 39

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          Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis.

          Fas antigen is a cell-surface protein that mediates apoptosis. It is expressed in various tissues including the thymus and has structural homology with a number of cell-surface receptors, including tumour necrosis factor receptor and nerve growth factor receptor. Mice carrying the lymphoproliferation (lpr) mutation have defects in the Fas antigen gene. The lpr 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.
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            Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family.

            The Fas antigen (Fas) belongs to the tumor necrosis factor (TNF)/nerve growth factor receptor family, and it mediates apoptosis. Using a soluble form of mouse Fas, prepared by fusion with human immunoglobulin Fc, Fas ligand was detected on the cell surface of a cytotoxic T cell hybridoma, PC60-d10S. A cell population that highly expresses Fas ligand was sorted using a fluorescence-activated cell sorter, and its cDNA was isolated from the sorted cells by expression cloning. The amino acid sequence indicated that Fas ligand is a type II transmembrane protein that belongs to the TNF family. The recombinant Fas ligand expressed in COS cells induced apoptosis in Fas-expressing target cells. Northern hybridization revealed that Fas ligand is expressed in activated splenocytes and thymocytes, consistent with its involvement in T cell-mediated cytotoxicity and in several nonlymphoid tissues, such as testis.
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              • Record: found
              • Abstract: not found
              • Article: not found

              Simplified mammalian DNA isolation procedure.

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                Author and article information

                Journal
                7581453
                10.1038/ng1195-294

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