論文 - 詳細
| RRC ID | 11102 |
|---|---|
| 著者 | Doumanis J, Wada K, Kino Y, Moore AW, Nukina N. |
| タイトル | RNAi screening in Drosophila cells identifies new modifiers of mutant huntingtin aggregation. |
| ジャーナル | PLoS One |
| Abstract |
The fruitfly Drosophila melanogaster is well established as a model system in the study of human neurodegenerative diseases. Utilizing RNAi, we have carried out a high-throughput screen for modifiers of aggregate formation in Drosophila larval CNS-derived cells expressing mutant human Huntingtin exon 1 fused to EGFP with an expanded polyglutamine repeat (62Q). 7200 genes, encompassing around 50% of the Drosophila genome, were screened, resulting in the identification of 404 candidates that either suppress or enhance aggregation. These candidates were subjected to secondary screening in normal length (18Q)-expressing cells and pruned to remove dsRNAs with greater than 10 off-target effects (OTEs). De novo RNAi probes were designed and synthesized for the remaining 68 candidates. Following a tertiary round of screening, 21 high confidence candidates were analyzed in vivo for their ability to modify mutant Huntingtin-induced eye degeneration and brain aggregation. We have established useful models for the study of human HD using the fly, and through our RNAi screen, we have identified new modifiers of mutant human Huntingtin aggregation and aggregate formation in the brain. Newly identified modifiers including genes related to nuclear transport, nucleotide processes, and signaling, may be involved in polyglutamine aggregate formation and Huntington disease cascades. |
| 巻・号 | 4(9) |
| ページ | e7275 |
| 公開日 | 2009-9-30 |
| DOI | 10.1371/journal.pone.0007275 |
| PMID | 19789644 |
| PMC | PMC2748703 |
| MeSH | Animals Drosophila Proteins Drosophila melanogaster / genetics* Exons False Positive Reactions Female Genome Huntingtin Protein Male Microscopy, Confocal / methods Microtubule-Associated Proteins / genetics* Mutation Peptides / genetics Phenotype RNA Interference* RNA, Double-Stranded / genetics Transgenes |
| IF | 2.74 |
| 引用数 | 47 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
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