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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 孔祥智(Hsiang-Chih Kung) | |
| dc.contributor.author | Wei-Ching Hsu | en |
| dc.contributor.author | 徐維璟 | zh_TW |
| dc.date.accessioned | 2021-06-15T02:25:48Z | - |
| dc.date.available | 2009-12-31 | |
| dc.date.copyright | 2009-09-15 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-08-18 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43677 | - |
| dc.description.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. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T02:25:48Z (GMT). No. of bitstreams: 1 ntu-98-R96449003-1.pdf: 769581 bytes, checksum: 8dbf4b1d0612549b304bd0b1389f7893 (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | Abstract……………………………………………………………… ii
Abstract (Chinese)…………………………………………………… iii Chapter I Introduction …………………………………………….. 1 1.1 Background information and related studies…………………. 1 Chapter II Material and Methods…………………………………. 7 2.1 Mice…………………………………………………………... 7 2.2 Surface marker detection by flow cytometer………………….. 7 2.3 Intracellular staining of Zap-70……………………………….. 8 2.4 Real-time PCR………………………………………………… 9 2.5 IFN-γ, IL-5, IL-10, and IL-13 detection by ELISA…………… 10 2.6 IL-4/2 functional bioassay…………………………………….. 11 2.7 Spleen CD4+ and CD8+ T cell isolation by panning…………... 12 2.8 T cell activation………………………………………………... 13 2.9 293T cell transfection…………………………………………. 14 2.10 Immunoprecipitation…………………………………………. 15 2.11 Western blot………………………………………………….. 16 Chapter III Experimental Results………………………………… 18 3.1 Altered T cell development in P358 mice……………………... 18 3.2 The expression of Zap-70 shows post-transcriptional down-regulation in P358 mice………………………………… 18 3.3 Impaired kinase activity of P358 Zap-70 in 293T cell………... 20 3.4 Reduced phosphorylation of Lat in P358 thymocyte………….. 20 3.5 Both Zap-70 wt and Zap-70P358 can dimerization……………… 21 3.6 TCR-mediated activation of T cell is deficient in P358 mice. 21 3.7 P358 CD4+ T cells produce Th2 cytokines……………………. 22 3.8 Summary………………………………………………………. 23 Chapter IV Discussion………………………………………………. 24 4.1 Post-transcriptional down-regulation of Zap-70P358…………... 24 4.2 The insistent results of phosphorylated Lat in thymocyte versus transfected 293 T cell………………………………….. 25 4.3 Dimerization of Zap-70……………………………………….. 27 4.4 P358 CD4+ T cell exhibits Th2-trended cytokine expression profiles………………………………………………………… 27 Reference…………………………………………………………….. 29 Chapter V Experimental Figures…………………………………… 37 Figures…………………………………………………………… 37 | |
| dc.language.iso | en | |
| dc.subject | T 細胞 | zh_TW |
| dc.subject | Zap-70 | zh_TW |
| dc.subject | ENU | zh_TW |
| dc.subject | T cell | en |
| dc.subject | ENU | en |
| dc.subject | Zap-70 | en |
| dc.title | 新穎Zap-70突變基因所引起的異常蛋白表現與功能 | zh_TW |
| dc.title | Novel mutant Zap-70 gene results in altered protein expression and function | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 伍安怡(An-Yi Wu),果伽蘭(Chia-Lam Kuo),李建國(Chien-Kuo Lee) | |
| dc.subject.keyword | Zap-70,ENU,T 細胞, | zh_TW |
| dc.subject.keyword | Zap-70,ENU,T cell, | en |
| dc.relation.page | 46 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-08-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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