TY - JOUR
T1 - Acute cerebellar knockdown of sgce reproduces salient features of myoclonus-dystonia (DYT11) in mice
AU - Washburn, Samantha G.
AU - Fremont, Rachel
AU - Moreno, M. Camila
AU - Angueyra, Chantal
AU - Khodakhah, Kamran
N1 - Funding Information:
of cerebellar dysfunction, supported by the aberrant activity recorded from DCN neurons and Purkinje
Publisher Copyright:
© 2019, eLife Sciences Publications Ltd. All rights reserved.
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.52101
DO - 10.7554/eLife.52101
M3 - Article
C2 - 31868164
AN - SCOPUS:85077790094
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e52101
ER -