文章基本信息

标题：Contribution of Fas to diabetes development
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作者：Alexei Y. Savinov ; Andrew Tcherepanov ; E. Allison Green 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：2
页码：628-632
DOI：10.1073/pnas.0237359100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Fas (Tnfrsf6, Apo-1, CD95) is a death receptor involved in apoptosis induced in many cell types. Fas have been shown to be expressed by insulin-producing beta cells in mice and humans. However, the importance of Fas in the development of autoimmune diabetes remains controversial. To further evaluate the importance of Fas in pathogenesis of diabetes, we generated NOD mice (nonobese diabetic mice developing spontaneous autoimmune diabetes) with beta cell-specific expression of a dominant-negative point mutation in a death domain of Fas, known as lprcg or Fascg. Spontaneous diabetes was significantly delayed in NOD mice expressing Fascg, and the effect depended on the expression level of the transgene. However, Fascg-bearing mice were still sensitive to diabetes transferred by splenocytes from overtly diabetic NOD mice. At the same time, Fascg expression did neutralize the accelerating effect of transgenic Fas-ligand expressed by the same beta cells. Thus, both Fas-dependent and -independent mechanisms are involved in beta cell destruction, but interference with the Fas pathway early in disease development may retard or prevent diabetes progression.