Abstract:
:TRAF6 is a key player at the cross-roads of development and immunity. The analysis of its in vivo molecular function is a great challenge since severe developmental defects and early lethality caused by Traf6 deficiency in knock-out mice interfere with analyses of the immune response. In this study we have used a new strategy to analyze the function of Traf6 in a zebrafish-Salmonella infectious disease model. In our approach the effect of a Traf6 translation-blocking morpholino was titrated down to avoid developmental defects and the response to infection under these conditions was studied using the combination of microarray analysis and whole transcriptome deep sequencing. Transcriptome profiling of the traf6 knock-down allowed the identification of a gene set whose responsiveness during infection is highly dependent on Traf6. Expression trend analysis based on the resulting datasets identified nine clusters of genes with characteristic transcription response profiles, demonstrating Traf6 has a dynamic role as a positive and negative regulator. Among the Traf6-dependent genes was a large set of well known anti-microbial and inflammatory genes. Additionally, we identified several genes which were not previously linked to a response to microbial infection, such as the fertility hormone gene gnrh2 and the DNA-damage regulated autophagy modulator 1 gene dram1. With the use of the zebrafish embryo model we have now analyzed the in vivo function of Traf6 in the innate immune response without interference of adaptive immunity.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
Stockhammer OW,Rauwerda H,Wittink FR,Breit TM,Meijer AH,Spaink HPdoi
10.1016/j.molimm.2010.08.011subject
Has Abstractpub_date
2010-11-01 00:00:00pages
179-90issue
1-3eissn
0161-5890issn
1872-9142pii
S0161-5890(10)00555-9journal_volume
48pub_type
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1016/j.molimm.2009.12.005
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2020-04-01 00:00:00