摘要
我们表明为他们导致 overexpression 显型的能力由 assaying 在果蝇为人的基因功能执行一幅系统的屏幕的可行性。相应于 236 人的基因的超过 1 500 根转基因的苍蝇线被建立了。总共, 51 根线能够得到建议人的基因是功能的显型。当我们发现类似的变异的显型也被主导的否定异种引起了,这些 heterologous 基因是机能上地相关的人的 ribosomal 蛋白质 L8 基因或由果蝇 RPL8 的 RNAi downregulation 的形式。显著地,果蝇 RPL8 异种能被野类型的人的 RPL8 救。我们也提供果蝇 RPL8 是表明小径的胰岛素的一个新成员的基因证据。在摘要,许多人的基因的功能出现到高度被保存,并且在果蝇识别他们的能力在 vivo 为人的抄本的大规模分析代表一个强大的基因工具。
We demonstrate the feasibility of performing a systematic screen for human gene functions in Drosophila by assaying for their ability to induce overexpression phenotypes. Over 1 500 transgenic fly lines corresponding to 236 human genes have been established. In all, 51 lines are capable of eliciting a phenotype suggesting that the human genes are functional. These heterologous genes are functionally relevant as we have found a similar mutant phenotype caused either by a dominant negative mutant form of the human ribosomal protein L8 gene or by RNAi downregulation of the Drosophila RPL8. Significantly, the Drosophila RPL8 mutant can be rescued by wild-type human RPL8. We also provide genetic evidence that Drosophila RPL8 is a new member of the insulin signaling pathway. In summary, the functions of many human genes appear to be highly conserved, and the ability to identify them in Drosophila represents a powerful genetic tool for large-scale analysis of human transcripts in vivo.
基金
We are grateful to Xizhi Ma, Junnian Zhou, Tianhong Xu, Xu Liu, Xu Ding, Yang Liu, Ying Peng, Congwu Chi, Yiying Shang, Mingyao Ying, Sheng Ding, Lei Sun, Lei Tian, Huanhu Zhu, Hua Huang, Hongmei Li, and Xiaomo Wu for cDNA constructs and partial transgenic work, and Lihui Zhou (East China University of Science and Technology, China) for scanning electron microscopy. We thank Duc Nguyen (Yale University, USA) for critical reading and editing of this manuscript. This work is supported by grants from the National Natural Science Foundation of China (Grant Nos. 30030080, 39970408 and 30470840), National Basic Research Program of China (973) (Grant No. 2006CB806700).
关键词
遗传基因
显性
GAL4/UAS
可行性
细胞
Drosophila, human gene, GAL4/UAS, genetic screen, RPL8, insulin signaling