[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-1-en-105":3,"doc-seo-200674-105":53,"doc-detail-200674-en":126},{"code":4,"msg":5,"data":6},0,"success",[7,14,19,24,29,34,39,44,49],{"id":8,"doc_module":9,"doc_module_name":10,"category_name":11,"show_sort_weight":12,"slug":13},11,1,"Template","Presentations",90,"presentations",{"id":15,"doc_module":9,"doc_module_name":10,"category_name":16,"show_sort_weight":17,"slug":18},12,"Resumes",80,"resumes",{"id":20,"doc_module":9,"doc_module_name":10,"category_name":21,"show_sort_weight":22,"slug":23},14,"Invoices",70,"invoices",{"id":25,"doc_module":9,"doc_module_name":10,"category_name":26,"show_sort_weight":27,"slug":28},15,"Posters",60,"posters",{"id":30,"doc_module":9,"doc_module_name":10,"category_name":31,"show_sort_weight":32,"slug":33},16,"Social Media",50,"social-media",{"id":35,"doc_module":9,"doc_module_name":10,"category_name":36,"show_sort_weight":37,"slug":38},17,"Forms",40,"forms",{"id":40,"doc_module":9,"doc_module_name":10,"category_name":41,"show_sort_weight":42,"slug":43},18,"Letters",30,"letters",{"id":45,"doc_module":9,"doc_module_name":10,"category_name":46,"show_sort_weight":47,"slug":48},21,"Paper Templates",5,"papers-templates",{"id":50,"doc_module":9,"doc_module_name":10,"category_name":51,"show_sort_weight":4,"slug":52},158,"General","general-158",{"code":4,"msg":54,"data":55},"ok",{"site_id":56,"language":57,"slug":58,"title":59,"keywords":60,"description":61,"schema_data":62,"social_meta":119,"head_meta":121,"extra_data":123,"updated_unix":125},105,"en","genetic-suppression-of-polyglutamine-toxicity-in-drosophila","Genetic Suppression of Polyglutamine Toxicity in Drosophila","","A Drosophila eye model for Huntington’s and other polyglutamine neurodegenerative diseases was used to identify genetic modifiers of degeneration driven by polyglutamine expression. From 7000 P-element insertions, suppressor strains revealed two suppressor genes, dHDJ1 and dTPR2, homologous to human HDJ1 and TPR2 and containing J-domain chaperone-related features. Suppression was verified in transgenic flies, including restoration of eye structure and pigmentation with continued polyglutamine aggregation.",{"@graph":63,"@context":118},[64,80,101],{"@type":65,"itemListElement":66},"BreadcrumbList",[67,71,74,77],{"item":68,"name":69,"@type":70,"position":9},"https://docshare.wps.com","Home","ListItem",{"item":72,"name":10,"@type":70,"position":73},"https://docshare.wps.com/template/",2,{"item":75,"name":51,"@type":70,"position":76},"https://docshare.wps.com/template/general/",3,{"item":78,"name":59,"@type":70,"position":79},"https://docshare.wps.com/template/genetic-suppression-of-polyglutamine-toxicity-in-drosophila/200674/",4,{"url":78,"name":59,"@type":81,"image":82,"author":87,"headline":59,"publisher":90,"fileFormat":93,"inLanguage":57,"description":61,"dateModified":94,"datePublished":95,"encodingFormat":93,"isAccessibleForFree":96,"interactionStatistic":97},"DigitalDocument",{"url":83,"@type":84,"width":85,"height":86},"https://docshare.wps.com/thumbnails/genetic-suppression-of-polyglutamine-toxicity-in-drosophila/200674.png","ImageObject",442,249,{"name":88,"@type":89},"Liam","Person",{"url":68,"name":91,"@type":92},"DocShare","Organization","application/vnd.openxmlformats-officedocument.wordprocessingml.document","2026-09-23","2026-09-04",true,{"@type":98,"interactionType":99,"userInteractionCount":73},"InteractionCounter",{"@type":100},"ViewAction",{"@type":102,"mainEntity":103},"FAQPage",[104,110,114],{"name":105,"@type":106,"acceptedAnswer":107},"What was the purpose of screening Drosophila for suppressors?","Question",{"text":108,"@type":109},"To find genetic factors that modify degeneration caused by polyglutamine expression in the fly eye.","Answer",{"name":111,"@type":106,"acceptedAnswer":112},"Which suppressor genes were identified from the P-element screen?",{"text":113,"@type":109},"Two suppressor genes were described: dHDJ1 and dTPR2.",{"name":115,"@type":106,"acceptedAnswer":116},"How was suppression of polyglutamine toxicity verified in transgenic flies?",{"text":117,"@type":109},"Transgenic flies showed restored external eye structure and pigmentation with suppressor insertions, while polyglutamine aggregates could still be detected.","https://schema.org",{"og:url":78,"og:type":120,"og:title":59,"og:site_name":91,"og:description":61},"article",{"robots":122,"canonical":78},"index,follow",{"doc_id":124,"site_id":56},200674,1790183492,{"code":4,"msg":5,"data":127},{"doc_id":124,"user_id":128,"nickname":88,"user_avatar":129,"doc_module":9,"category_id":50,"category_name":51,"doc_title":59,"doc_description":61,"doc_content":130,"file_id":131,"file_url":132,"file_type":133,"file_size":134,"view_count":73,"is_deleted":4,"is_public":9,"is_downloadable":9,"audit_status":9,"page_count":35,"language":135,"language_code":57,"site_id":56,"html_lang":57,"table_of_contents":136,"faqs":137,"seo_title":138,"seo_description":61,"update_tm":139,"read_time":140},8796095461564,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Genetic Suppression of Polyglutamine Toxicity in Drosophila\nParsa Kazemi-Esfarjani, * Seymour Benzer\nA Drosophila model for Huntington's and other polyglutamine diseases was used to screen for genetic factors modifying the degeneration caused by expression of polyglutamine in the eye. Among 7000 P-element insertions, several suppressor strains were isolated, two of which led to the discovery of the suppressor genes described here. The predicted product of one, dHDJ1, is homologous to human heat shock protein 40/HDJ1. That of the second, dTPR2, is homologous to the human tetratricopeptide repeat protein 2. Each of these molecules contains a chaperone-related J domain. Their suppression of polyglutamine toxicity was verified in transgenic flies.\nDivision of Biology, California Institute of Technology, Pasadena, CA 91125, USA. \u000b*   To whom correspondence should be addressed. E-mail: \u0013 HYPERLINK \"mailto:parsa@its.caltech.edu\" \u0014parsa@its.caltech.edu\u0015\nExpanded polyCAG tracts in the genes for Huntington's disease (HD) and at least seven other disorders are associated with hereditary neurodegeneration (\u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF1\" \u00141\u0015). The polyCAGs are translated to polyglutamines, which form cytoplasmic and/or nuclear aggregates and produce toxic effects (\u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF1\" \u00141\u0015, \u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF2\" \u00142\u0015). One approach to the identification of proteins that can modify polyglutamine aggregation and toxicity is the isolation of enhancer and suppressor genes. For this purpose, the Drosophila eye offers a sensitive model system (\u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF3\" \u00143\u0015, \u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF4\" \u00144\u0015). In a candidate gene approach, a baculovirus antiapoptotic gene, p35, and a human heat shock protein (HSP70, encoded by the HSPA1L gene) suppressed polyglutamine-dependent degeneration in the eye (\u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF3\" \u00143\u0015, \u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF5\" \u00145\u0015). Here an alternative approach is described: screening the fly genome for genes that dominantly modify the toxicity of polyglutamine.\nUsing a polymerase chain reaction (PCR) method, we synthesized polyCAGs of short (20 CAGs) and expanded (127 CAGs) lengths (\u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF6\" \u00146\u0015). These were placed in transgenic constructs cis to the yeast upstream activating sequence (UAS). Their expression was activated in genetic crosses trans to the yeast GAL4 transcription factor, expression of which was in turn regulated by the eye-specific promoter GMR upstream of the yeast GAL4 cDNA (\u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF7\" \u00147-9\u0015). GMR is composed of five tandem copies of a response element derived from the rhodopsin 1 gene promoter, a binding site for the eye-specific transcription factor GLASS (\u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF10\" \u001410\u0015). This promoter enhances the expression of the reporter gene in all retinal cell types as they develop. Flies carrying GMR-GAL4 were crossed with three independently generated UAS-polyCAG transgenic lines carrying the short 20-CAG repeat (UAS-20Q) and with those containing the expanded 127-CAG repeat (UAS-127Q), and in all cases were tagged with a hemagglutinin (HA) epitope sequence (\u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837\" \\l \"RF11\" \u001411\u0015).\nIn all three GMR-GAL4/UAS-20Q lines, flies eclosed as adults with eyes that were morphologically normal and had normal pigment distribution. In contrast, the three lines of GMR-GAL4/UAS-127Q had severely abnormal eyes (\u0013 HYPERLINK \"http://www.sciencemag.org/cgi/content/full/287/5459/1837","cbCaiuA4Tr5278Ww","https://ap.wps.com/l/cbCaiuA4Tr5278Ww","docx",148530,"English","# Genetic Suppression of Polyglutamine Toxicity in Drosophila\n## Disease model and screening strategy\n## Suppressor genes dHDJ1 and dTPR2\n## Transgenic validation and eye phenotype","[{\"question\":\"What was the purpose of screening Drosophila for suppressors?\",\"answer\":\"To find genetic factors that modify degeneration caused by polyglutamine expression in the fly eye.\"},{\"question\":\"Which suppressor genes were identified from the P-element screen?\",\"answer\":\"Two suppressor genes were described: dHDJ1 and dTPR2.\"},{\"question\":\"How was suppression of polyglutamine toxicity verified in transgenic flies?\",\"answer\":\"Transgenic flies showed restored external eye structure and pigmentation with suppressor insertions, while polyglutamine aggregates could still be detected.\"}]","Genetic Suppression of Polyglutamine Toxicity in Drosophila | DOCX",1788509792,6]