权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Genetic approaches to elucidate mechanism for action of dioxin receptor using Drosophila

使用果蝇阐明二恶英受体作用机制的遗传方法

基本信息

批准号：
15510052
负责人：
ADACHI Takashi
金额：
$ 2.24万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Dioxins show a chronic toxicity, teratogenicity and carcinogenicity. Its atmospheric accumulation is therefore one of the current environmental problems to be resolved. Intracellular dioxins bind to its receptor Ahr which is a transcription factor and act together with an allied protein Arnt. However the pathways regulating apoptosis, teratogenicity, and carcinogenicity have not fully been revealed. We have thus used a genetically amenable model organism Drosophila to clarify these mechanisms. We found that ectopic action of Spineless, a Drosophila homolog of dioxin receptor induces a severe apoptosis. Using this phenotype, we tried to study about the following three issues.1. Analysis of signaling pathways to lead to apoptosis induced by Spineless.2. Effect of JNK, a environmental stress-activated signal transducer, on action of Spineless.3. Isolation and analysis of new mutant which suppresses apoptosis induced by Spineless.Results :1. Ectopic action of Spineless in the wing leads to ectopic occurrence of the leg/antenna through elevation of Distal-less expression. The apoptosis is dependent on this homeotic transformation. The key to induce apoptosis is reduction of cell-cell interaction mediated by a novel LRR family protein Fish-lips.2. Apoptosis induced by Spineless strongly depends on JNK activity, whereas both the homeotic transformation and alteration of cell-cell interaction by Spineless were not affected by JNK.3. A novel mutant "Suppressor of spineless expression (Sussex)" was isolated and mapped to the second chromosome.

二恶英具有慢性毒性、致畸性和致癌性。因此，其在大气中的积累是当前有待解决的环境问题之一。细胞内二恶英与其转录因子受体Ahr结合，并与同源蛋白Arnt共同作用。然而，调节细胞凋亡、致畸性和致癌性的途径尚未完全揭示。因此，我们使用了一种遗传上适合的模式生物果蝇来阐明这些机制。我们发现，果蝇的二恶英受体同源物Spineless的异位作用诱导了严重的细胞凋亡。利用这一表型，我们试图研究以下三个问题.分析导致Spineless诱导细胞凋亡的信号通路. JNK是环境应激激活的信号转导子，对Spineless作用的影响.分离并分析了抑制Spineless诱导细胞凋亡的新突变体。翼中无刺的异位作用通过无远端表达的升高导致腿/触角的异位发生。细胞凋亡依赖于这种同源异型转化。结论：1. LRR家族新蛋白Fish-lips介导的细胞间相互作用减少是诱导细胞凋亡的关键。Spineless诱导的细胞凋亡强烈依赖于JNK活性，而Spineless对同源异型转化和细胞间相互作用的改变均不受JNK的影响.分离到一个新的突变体“Suppressor of spineless expression（Sussex）”，并定位于第二染色体。