Acute cerebellar knockdown of Sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice
| Autor: | Maria Camila Moreno-Escobar, Rachel Fremont, Chantal Angueyra, Kamran Khodakhah, Samantha Washburn |
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| Rok vydání: | 2019 |
| Předmět: |
DYT11
0301 basic medicine Genetically modified mouse Cerebellum QH301-705.5 Science General Biochemistry Genetics and Molecular Biology Small hairpin RNA 03 medical and health sciences 0302 clinical medicine myoclonus dystonia SGCE Basal ganglia alcohol responsive dystonia medicine Biology (General) 030304 developmental biology Dystonia 0303 health sciences Gene knockdown General Immunology and Microbiology business.industry General Neuroscience General Medicine medicine.disease nervous system diseases 030104 developmental biology medicine.anatomical_structure Medicine medicine.symptom business Neuroscience Myoclonus 030217 neurology & neurosurgery |
| Zdroj: | eLife, Vol 8 (2019) |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.52101 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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