Disruption of SMN function by ectopic expression of the human SMN gene in Drosophila.
Spinal muscular atrophy is a neurodegenerative disorder caused by mutations or deletions in the survival motor neuron (SMN) gene. We have cloned the Drosophila ortholog of SMN (DmSMN) and disrupted its function by ectopically expressing human SMN. This leads to pupal lethality caused by a dominant-n...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2000
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| _version_ | 1797072344430149632 |
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| author | Miguel-Aliaga, I Chan, Y Davies, K van den Heuvel, M |
| author_facet | Miguel-Aliaga, I Chan, Y Davies, K van den Heuvel, M |
| author_sort | Miguel-Aliaga, I |
| collection | OXFORD |
| description | Spinal muscular atrophy is a neurodegenerative disorder caused by mutations or deletions in the survival motor neuron (SMN) gene. We have cloned the Drosophila ortholog of SMN (DmSMN) and disrupted its function by ectopically expressing human SMN. This leads to pupal lethality caused by a dominant-negative effect, whereby human SMN may bind endogenous DmSMN resulting in non-functional DmSMN/human SMN hetero-complexes. Ectopic expression of truncated versions of DmSMN and yeast two-hybrid analysis show that the C-terminus of SMN is necessary and sufficient to replicate this effect. We have therefore generated a system which can be utilized to carry out suppressor and high-throughput screens, and provided in vivo evidence for the importance of SMN oligomerization for SMN function at the level of an organism as a whole. |
| first_indexed | 2024-03-06T23:06:27Z |
| format | Journal article |
| id | oxford-uuid:63f91e07-7792-4813-abd8-3446f3d4ce9e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:06:27Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:63f91e07-7792-4813-abd8-3446f3d4ce9e2022-03-26T18:16:10ZDisruption of SMN function by ectopic expression of the human SMN gene in Drosophila.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:63f91e07-7792-4813-abd8-3446f3d4ce9eEnglishSymplectic Elements at Oxford2000Miguel-Aliaga, IChan, YDavies, Kvan den Heuvel, MSpinal muscular atrophy is a neurodegenerative disorder caused by mutations or deletions in the survival motor neuron (SMN) gene. We have cloned the Drosophila ortholog of SMN (DmSMN) and disrupted its function by ectopically expressing human SMN. This leads to pupal lethality caused by a dominant-negative effect, whereby human SMN may bind endogenous DmSMN resulting in non-functional DmSMN/human SMN hetero-complexes. Ectopic expression of truncated versions of DmSMN and yeast two-hybrid analysis show that the C-terminus of SMN is necessary and sufficient to replicate this effect. We have therefore generated a system which can be utilized to carry out suppressor and high-throughput screens, and provided in vivo evidence for the importance of SMN oligomerization for SMN function at the level of an organism as a whole. |
| spellingShingle | Miguel-Aliaga, I Chan, Y Davies, K van den Heuvel, M Disruption of SMN function by ectopic expression of the human SMN gene in Drosophila. |
| title | Disruption of SMN function by ectopic expression of the human SMN gene in Drosophila. |
| title_full | Disruption of SMN function by ectopic expression of the human SMN gene in Drosophila. |
| title_fullStr | Disruption of SMN function by ectopic expression of the human SMN gene in Drosophila. |
| title_full_unstemmed | Disruption of SMN function by ectopic expression of the human SMN gene in Drosophila. |
| title_short | Disruption of SMN function by ectopic expression of the human SMN gene in Drosophila. |
| title_sort | disruption of smn function by ectopic expression of the human smn gene in drosophila |
| work_keys_str_mv | AT miguelaliagai disruptionofsmnfunctionbyectopicexpressionofthehumansmngeneindrosophila AT chany disruptionofsmnfunctionbyectopicexpressionofthehumansmngeneindrosophila AT daviesk disruptionofsmnfunctionbyectopicexpressionofthehumansmngeneindrosophila AT vandenheuvelm disruptionofsmnfunctionbyectopicexpressionofthehumansmngeneindrosophila |