Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model
A polyglutamine expansion in the huntingtin (HTT) gene causes neurodegeneration in Huntington’s disease (HD), but the in vivo function of the native protein (Htt) is largely unknown. Numerous biochemical and in vitro studies have suggested a role for Htt in neuronal development, synaptic function an...
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| Format: | Article |
| Language: | en_US |
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Company of Biologists
2010
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| Online Access: | http://hdl.handle.net/1721.1/56290 https://orcid.org/0000-0001-5576-2887 |
| _version_ | 1811082778425425920 |
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| author | Littleton, J. Troy Zhang, Sheng Saraswati, Sudipta Feany, Mel B. Perrimon, Norbert |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Littleton, J. Troy Zhang, Sheng Saraswati, Sudipta Feany, Mel B. Perrimon, Norbert |
| author_sort | Littleton, J. Troy |
| collection | MIT |
| description | A polyglutamine expansion in the huntingtin (HTT) gene causes neurodegeneration in Huntington’s disease (HD), but the in vivo function of the native protein (Htt) is largely unknown. Numerous biochemical and in vitro studies have suggested a role for Htt in neuronal development, synaptic function and axonal trafficking. To test these models, we generated a null mutant in the putative Drosophila HTT homolog (htt, hereafter referred to asdhtt) and, surprisingly, found that dhtt mutant animals are viable with no obvious developmental defects. Instead, dhtt is required for maintaining the mobility and long-term survival of adult animals, and for modulating axonal terminal complexity in the adult brain. Furthermore, removing endogenous dhtt significantly accelerates the neurodegenerative phenotype associated with a Drosophila model of polyglutamine Htt toxicity (HD-Q93), providing in vivo evidence that disrupting the normal function of Htt might contribute to HD pathogenesis. |
| first_indexed | 2024-09-23T12:08:50Z |
| format | Article |
| id | mit-1721.1/56290 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:08:50Z |
| publishDate | 2010 |
| publisher | Company of Biologists |
| record_format | dspace |
| spelling | mit-1721.1/562902022-10-01T08:28:29Z Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model Littleton, J. Troy Zhang, Sheng Saraswati, Sudipta Feany, Mel B. Perrimon, Norbert Massachusetts Institute of Technology. Department of Biology Littleton, J. Troy Littleton, J. Troy Saraswati, Sudipta A polyglutamine expansion in the huntingtin (HTT) gene causes neurodegeneration in Huntington’s disease (HD), but the in vivo function of the native protein (Htt) is largely unknown. Numerous biochemical and in vitro studies have suggested a role for Htt in neuronal development, synaptic function and axonal trafficking. To test these models, we generated a null mutant in the putative Drosophila HTT homolog (htt, hereafter referred to asdhtt) and, surprisingly, found that dhtt mutant animals are viable with no obvious developmental defects. Instead, dhtt is required for maintaining the mobility and long-term survival of adult animals, and for modulating axonal terminal complexity in the adult brain. Furthermore, removing endogenous dhtt significantly accelerates the neurodegenerative phenotype associated with a Drosophila model of polyglutamine Htt toxicity (HD-Q93), providing in vivo evidence that disrupting the normal function of Htt might contribute to HD pathogenesis. 2010-07-14T14:51:01Z 2010-07-14T14:51:01Z 2009-05 2008-04 Article http://purl.org/eprint/type/Report 1754-8403 1754-8411 http://hdl.handle.net/1721.1/56290 Zhang, Sheng et al. “Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model.” Disease Models & Mechanisms 2.5-6 (2009): 247-266. https://orcid.org/0000-0001-5576-2887 en_US http://dx.doi.org/10.1242/dmm.000653 Disease Models and Mechanisms Attribution-Noncommercial-Share Alike 3.0 Unported http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Company of Biologists J. Troy Littleton |
| spellingShingle | Littleton, J. Troy Zhang, Sheng Saraswati, Sudipta Feany, Mel B. Perrimon, Norbert Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model |
| title | Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model |
| title_full | Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model |
| title_fullStr | Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model |
| title_full_unstemmed | Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model |
| title_short | Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model |
| title_sort | inactivation of drosophila huntingtin affects long term adult functioning and the pathogenesis of a huntington s disease model |
| url | http://hdl.handle.net/1721.1/56290 https://orcid.org/0000-0001-5576-2887 |
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