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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43677
Title: | 新穎Zap-70突變基因所引起的異常蛋白表現與功能 Novel mutant Zap-70 gene results in altered protein expression and function |
Authors: | Wei-Ching Hsu 徐維璟 |
Advisor: | 孔祥智(Hsiang-Chih Kung) |
Keyword: | Zap-70,ENU,T 細胞, Zap-70,ENU,T cell, |
Publication Year : | 2009 |
Degree: | 碩士 |
Abstract: | T-cell receptor ζ chain-associated protein kinase 70 (Zap-70) is important for T cell development and activation. Both Zap-70-deficient humans and mice suffer from severe combined immunodeficiency (SCID) due to highly deficient T cell development. In Zap-70-knockout mice, intrathymic T cell developmental is blocked at the CD4+CD8+ double positive stage and no αβ-TCR+ T cells are seen. Here we made use of an ENU-induced Zap-70 mutant mouse, P358, characterized by a point mutation that results in a C563S amino acid change in the kinase domain. P358 mice are different from Zap-70-null mice in that significant numbers of CD4+ and CD8+ T cells develop. Zap-70 mRNA is expressed at similar levels in wildtype and P358 T cells, but Zap-70 protein expression in P358 is three- to four-fold reduced when compared to wildtype. Using TCR-stimulated P358 thymocytes or spleen cells, there is significant but reduced Lat phosphorylation. Functional studies reveal that P358 CD4+ T cell shows Th2 cytokines. In addition, the proliferation of P358 CD4+ and CD8+ T cells are defective upon stimulation by plate-bound anti-CD3. The P358 ENU mutant is therefore a Zap-70 hypomorphic model and has revealed new aspects of how the single C563S amino acid change affects protein turnover or function. This novel mouse mutant model is a tool that may help probe questions such as differential thresholds of Zap-70-dependent pleiotropic functions, mechanism of intrathymic selection processes, and how dysregulated immune cells and immune responses are generated. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43677 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 免疫學研究所 |
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