Immunological and Pathological Consequences of Mutations in both Fas and Fas Ligand
Thelprmutation in mice results in premature termination of transcription of the gene encoding the apoptosis-signaling receptor Fas. As a result,lprmice develop severe lymphoproliferation and lupus-like autoantibodies. Growing evidence suggests that thelprmutation is “leaky” and that low levels of Fa...
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Published in | Cellular immunology Vol. 186; no. 1; pp. 8 - 17 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier Inc
25.05.1998
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Subjects | |
Online Access | Get full text |
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Summary: | Thelprmutation in mice results in premature termination of transcription of the gene encoding the apoptosis-signaling receptor Fas. As a result,lprmice develop severe lymphoproliferation and lupus-like autoantibodies. Growing evidence suggests that thelprmutation is “leaky” and that low levels of Fas are expressed inlprmice. To determine if Fas expressed inlprmice is contributing to apoptosis we generated a novel strain of mice (B6/lprgld) which is homozygous for both thelprmutation and thegldmutation which encodes nonfunctional Fas ligand (FasL) protein. If low levels of Fas in B6/lprmice contribute to apoptosis and lessen the severity of disease, the B6/lprgldmice, which also lack functional FasL, would be expected to develop a more severe form of disease than B6/lprmice. Our results revealed no significant increase in either lymphoproliferation or autoimmunity in B6/lprgldmice compared to B6/lpror B6/gldmice. Additionally, no increase in surface expression of Fas was detected by flow cytometry on B6/lprgldlymphocytes compared to B6/lprlymphocytes. However, histological examination of B6/lprgldliver revealed a marked increase in lymphocytic infiltration, compared to livers of B6/lprand B6/gldmice. Our results suggest that, while low levels of Fas inlprmice may not be contributing to amelioration of lymphoproliferation or autoimmunity, they may be partially protecting the liver from abnormalities which arise in the absence of Fas-mediated apoptosis. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0008-8749 1090-2163 |
DOI: | 10.1006/cimm.1998.1290 |