國家衛生研究院 NHRI:Item 3990099045/12281
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    題名: Functional analysis of a novel gene X causing small eye phenotype through JNK-dependent apoptosis pathway
    作者: Suresh, D;Ching, Y;Lin, M;Liao, B
    貢獻者: Institute of Population Health Sciences
    摘要: Introduction: A bioinformatics work comprising coexpression gene network in the mouse was built based on microarray and RNA-Seq platforms, revealed an unexplored gene X which might play a role in retinal development. X contains an evolutionary conserved protein domain with a function of oxidative stress resistance by scavenging reactive oxygen species (ROS), but the gene function remains to be explored. The aim of this study was to elucidate X gene function, mechanism and its role in eye development using Drosophila and mice as a model organism.Materials and Methods: The GAL4-UAS system were used to speci fi cally knockdown homologue of X in the eye of Drosophila and resulted in the small eye phenotype. Various genetic crosses were performed to analyze the phenotype were mediated through apoptotic or autophagy pathway. The mice homologous gene knockout was generated using CRISPR/Cas9 technology. Results: Knockdown of X in Drosophila resulted in severe small eye phenotype, and the knockout mice were blind. In Drosophila, P35 baculovirus overexpression (active caspase inhibitor) and knockdown of pro-apoptotic genes showed complete rescue of small eye phenotype. To further identify the exact apoptotic pathway, various players involved in JUN N-terminal kinase (JNK) apoptosis pathway rescue the small eye phenotype. Conclusions: The small eye phenotype of X could be involved in the JNK-mediated apoptosis pathway. Our future studies would be to prove JNK dependent apoptosis, the role of ROS, mutagenesis study to explore more about the function of X.
    日期: 2019-07
    關聯: European Journal of Human Genetics. 2019 Jul;27(Suppl. 1):479.
    Link to: https://doi.org/10.1038/s41431-019-0404-7
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1018-4813&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000489313104102
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