Polyglutamine-induced neurodegeneration in SCA3 is not mitigated by non-expanded ataxin-3: Conclusions from double-transgenic mouse models
A crucial question in polyQ-induced neurodegeneration is the influence of wild type protein on the formation of aggregates and toxicity. Recently it was shown that non-expanded ataxin-3 protein mitigated neurodegeneration in a Drosophila and mouse model of SCA3. We now explored the effects of overex...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-04-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996110000070 |
| _version_ | 1818573136798416896 |
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| author | Jeannette Hübener Olaf Riess |
| author_facet | Jeannette Hübener Olaf Riess |
| author_sort | Jeannette Hübener |
| collection | DOAJ |
| description | A crucial question in polyQ-induced neurodegeneration is the influence of wild type protein on the formation of aggregates and toxicity. Recently it was shown that non-expanded ataxin-3 protein mitigated neurodegeneration in a Drosophila and mouse model of SCA3. We now explored the effects of overexpressing non-expanded ataxin-3 with 15Q in a SCA3 transgenic mouse model with 70 polyglutamine repeats. These double-transgenic mice (dt) developed neurological symptoms with premature death at the age of 6 months comparable to the single-transgenic (st) SCA3 disease model. Furthermore, immunohistochemistry revealed similar localization and distribution of nuclear aggregates in dt- and st-mutant SCA3 mice. In a second dt-mutant mouse model, coexpression of ataxin-3 with 148Q attached to a nuclear export signal, which usually diminishes the phenotype, did even reinforce toxic effects of mutant expanded ataxin-3. We therefore conclude that overexpressing wild type ataxin-3 or mutant ataxin-3 with NES are not striking suppressors of polyglutamine-induced neurodegeneration and have thus no potential for future gene therapeutic interventions in SCA3. |
| first_indexed | 2024-12-15T00:07:03Z |
| format | Article |
| id | doaj.art-effbf59e43104dba89300fbe38efacbe |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-15T00:07:03Z |
| publishDate | 2010-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-effbf59e43104dba89300fbe38efacbe2022-12-21T22:42:42ZengElsevierNeurobiology of Disease1095-953X2010-04-01381116124Polyglutamine-induced neurodegeneration in SCA3 is not mitigated by non-expanded ataxin-3: Conclusions from double-transgenic mouse modelsJeannette Hübener0Olaf Riess1Corresponding author. Department of Medical Genetics, University of Tuebingen, Calwerstrasse 7, 72076 Tuebingen, Germany. Fax: +49 7071 295171.; Department of Medical Genetics, University of Tuebingen, Tuebingen, GermanyDepartment of Medical Genetics, University of Tuebingen, Tuebingen, GermanyA crucial question in polyQ-induced neurodegeneration is the influence of wild type protein on the formation of aggregates and toxicity. Recently it was shown that non-expanded ataxin-3 protein mitigated neurodegeneration in a Drosophila and mouse model of SCA3. We now explored the effects of overexpressing non-expanded ataxin-3 with 15Q in a SCA3 transgenic mouse model with 70 polyglutamine repeats. These double-transgenic mice (dt) developed neurological symptoms with premature death at the age of 6 months comparable to the single-transgenic (st) SCA3 disease model. Furthermore, immunohistochemistry revealed similar localization and distribution of nuclear aggregates in dt- and st-mutant SCA3 mice. In a second dt-mutant mouse model, coexpression of ataxin-3 with 148Q attached to a nuclear export signal, which usually diminishes the phenotype, did even reinforce toxic effects of mutant expanded ataxin-3. We therefore conclude that overexpressing wild type ataxin-3 or mutant ataxin-3 with NES are not striking suppressors of polyglutamine-induced neurodegeneration and have thus no potential for future gene therapeutic interventions in SCA3.http://www.sciencedirect.com/science/article/pii/S0969996110000070Ataxin-3Disease modificationDouble-transgenic miceMouse modelPolyglutamine diseaseSpinocerebellar ataxia type 3 |
| spellingShingle | Jeannette Hübener Olaf Riess Polyglutamine-induced neurodegeneration in SCA3 is not mitigated by non-expanded ataxin-3: Conclusions from double-transgenic mouse models Neurobiology of Disease Ataxin-3 Disease modification Double-transgenic mice Mouse model Polyglutamine disease Spinocerebellar ataxia type 3 |
| title | Polyglutamine-induced neurodegeneration in SCA3 is not mitigated by non-expanded ataxin-3: Conclusions from double-transgenic mouse models |
| title_full | Polyglutamine-induced neurodegeneration in SCA3 is not mitigated by non-expanded ataxin-3: Conclusions from double-transgenic mouse models |
| title_fullStr | Polyglutamine-induced neurodegeneration in SCA3 is not mitigated by non-expanded ataxin-3: Conclusions from double-transgenic mouse models |
| title_full_unstemmed | Polyglutamine-induced neurodegeneration in SCA3 is not mitigated by non-expanded ataxin-3: Conclusions from double-transgenic mouse models |
| title_short | Polyglutamine-induced neurodegeneration in SCA3 is not mitigated by non-expanded ataxin-3: Conclusions from double-transgenic mouse models |
| title_sort | polyglutamine induced neurodegeneration in sca3 is not mitigated by non expanded ataxin 3 conclusions from double transgenic mouse models |
| topic | Ataxin-3 Disease modification Double-transgenic mice Mouse model Polyglutamine disease Spinocerebellar ataxia type 3 |
| url | http://www.sciencedirect.com/science/article/pii/S0969996110000070 |
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