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Using Zebrafish as the Animal Model for Studying the Roles of Chop uORF on the Development
Date Issued
2007
Date
2007
Author(s)
Liu, Chia-Hung
DOI
zh-TW
Abstract
Abstract:
The upstream open reading frame (uORF), which has the inhibitory effect on the translation of the downstream gene, has been found in the 5’-untranslated region(5’-UTR) of many genes. Among the genes with uORF, most of them are responsible for crucial roles in the cell and need to be regulated precisely. However, the studies on uORF are
still executed mainly in vitro. In addition, the roles of uORF on the development are not clear. To investigate the in vivo role of Chop uORF on the development, we try to use the zebrafish, an excellent animal model for development study, for our study. In this study, we found that the uORF of human Chop gene could also exhibit its inhibitory effect in the zebrafish. By comparing the cDNA sequences, we found that uORF are conserved among many species . As the results of mutation experiment revealed, the two AUGs conserved in the uORF sequence among species were both involved in the inhibitory effects of uORF. The inhibitory ability of Chop uORF was shown to be under regulation by the temperature stress and knockdown experiments, in which the translational inhibition exerted by uORF was reduced in abnormally-developing embryos, indicating that the Chop uORF might be involved in the development. In the mRNA overexpression experiment and TUNEL assay, the results
suggested that Chop might play a role in the development by
influencing axis formation and apoptosis. The results showed that zebrafish might be a feasible animal model for investigating the in vivo function of uORF and its role in the development.
The upstream open reading frame (uORF), which has the inhibitory effect on the translation of the downstream gene, has been found in the 5’-untranslated region(5’-UTR) of many genes. Among the genes with uORF, most of them are responsible for crucial roles in the cell and need to be regulated precisely. However, the studies on uORF are
still executed mainly in vitro. In addition, the roles of uORF on the development are not clear. To investigate the in vivo role of Chop uORF on the development, we try to use the zebrafish, an excellent animal model for development study, for our study. In this study, we found that the uORF of human Chop gene could also exhibit its inhibitory effect in the zebrafish. By comparing the cDNA sequences, we found that uORF are conserved among many species . As the results of mutation experiment revealed, the two AUGs conserved in the uORF sequence among species were both involved in the inhibitory effects of uORF. The inhibitory ability of Chop uORF was shown to be under regulation by the temperature stress and knockdown experiments, in which the translational inhibition exerted by uORF was reduced in abnormally-developing embryos, indicating that the Chop uORF might be involved in the development. In the mRNA overexpression experiment and TUNEL assay, the results
suggested that Chop might play a role in the development by
influencing axis formation and apoptosis. The results showed that zebrafish might be a feasible animal model for investigating the in vivo function of uORF and its role in the development.
Subjects
斑馬魚
發育
uORF
zebrafish
chop
development
upstream open reading frame
Type
other
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Name
ntu-96-R94b43032-1.pdf
Size
23.31 KB
Format
Adobe PDF
Checksum
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