Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice
Myoclonus dystonia (DYT11) is a movement disorder caused by loss-of-function mutations in SGCE and characterized by involuntary jerking and dystonia that frequently improve after drinking alcohol. Existing transgenic mouse models of DYT11 exhibit only mild motor symptoms, possibly due to rodent-spec...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/52101 |
| _version_ | 1811253242113294336 |
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| author | Samantha Washburn Rachel Fremont Maria Camila Moreno-Escobar Chantal Angueyra Kamran Khodakhah |
| author_facet | Samantha Washburn Rachel Fremont Maria Camila Moreno-Escobar Chantal Angueyra Kamran Khodakhah |
| author_sort | Samantha Washburn |
| collection | DOAJ |
| description | Myoclonus dystonia (DYT11) is a movement disorder caused by loss-of-function mutations in SGCE and characterized by involuntary jerking and dystonia that frequently improve after drinking alcohol. Existing transgenic mouse models of DYT11 exhibit only mild motor symptoms, possibly due to rodent-specific developmental compensation mechanisms, which have limited the study of neural mechanisms underlying DYT11. To circumvent potential compensation, we used short hairpin RNA (shRNA) to acutely knock down Sgce in the adult mouse and found that this approach produced dystonia and repetitive, myoclonic-like, jerking movements in mice that improved after administration of ethanol. Acute knockdown of Sgce in the cerebellum, but not the basal ganglia, produced motor symptoms, likely due to aberrant cerebellar activity. The acute knockdown model described here reproduces the salient features of DYT11 and provides a platform to study the mechanisms underlying symptoms of the disorder, and to explore potential therapeutic options. |
| first_indexed | 2024-04-12T16:47:52Z |
| format | Article |
| id | doaj.art-409174e8749b4def9ee124d14457c827 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:47:52Z |
| publishDate | 2019-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-409174e8749b4def9ee124d14457c8272022-12-22T03:24:30ZengeLife Sciences Publications LtdeLife2050-084X2019-12-01810.7554/eLife.52101Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in miceSamantha Washburn0https://orcid.org/0000-0001-8317-1558Rachel Fremont1Maria Camila Moreno-Escobar2Chantal Angueyra3Kamran Khodakhah4https://orcid.org/0000-0001-7905-5335Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United StatesDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United StatesDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United StatesDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United StatesDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United StatesMyoclonus dystonia (DYT11) is a movement disorder caused by loss-of-function mutations in SGCE and characterized by involuntary jerking and dystonia that frequently improve after drinking alcohol. Existing transgenic mouse models of DYT11 exhibit only mild motor symptoms, possibly due to rodent-specific developmental compensation mechanisms, which have limited the study of neural mechanisms underlying DYT11. To circumvent potential compensation, we used short hairpin RNA (shRNA) to acutely knock down Sgce in the adult mouse and found that this approach produced dystonia and repetitive, myoclonic-like, jerking movements in mice that improved after administration of ethanol. Acute knockdown of Sgce in the cerebellum, but not the basal ganglia, produced motor symptoms, likely due to aberrant cerebellar activity. The acute knockdown model described here reproduces the salient features of DYT11 and provides a platform to study the mechanisms underlying symptoms of the disorder, and to explore potential therapeutic options.https://elifesciences.org/articles/52101DYT11myoclonus dystoniaalcohol responsive dystonia |
| spellingShingle | Samantha Washburn Rachel Fremont Maria Camila Moreno-Escobar Chantal Angueyra Kamran Khodakhah Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice eLife DYT11 myoclonus dystonia alcohol responsive dystonia |
| title | Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice |
| title_full | Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice |
| title_fullStr | Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice |
| title_full_unstemmed | Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice |
| title_short | Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice |
| title_sort | acute cerebellar knockdown of sgce reproduces salient features of myoclonus dystonia dyt11 in mice |
| topic | DYT11 myoclonus dystonia alcohol responsive dystonia |
| url | https://elifesciences.org/articles/52101 |
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