Deleting Mecp2 from the cerebellum rather than its neuronal subtypes causes a delay in motor learning in mice
| Autor: | Tao Lin, Olivia A. Kim, Huda Y. Zoghbi, Shogo Ohmae, Ling-jie He, Roy V. Sillitoe, Nathan P. Achilly, Gregory J. Wojaczynski, Javier F. Medina |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Cerebellum Time Factors cerebellum Mouse QH301-705.5 Methyl-CpG-Binding Protein 2 Science Short Report Rett syndrome Neurological disorder Motor Activity General Biochemistry Genetics and Molecular Biology MECP2 Mice 03 medical and health sciences 0302 clinical medicine Cortex (anatomy) Basal ganglia medicine Animals Humans Learning Biology (General) MeCP2 Mice Knockout Neurons General Immunology and Microbiology business.industry General Neuroscience General Medicine medicine.disease nervous system diseases Disease Models Animal 030104 developmental biology medicine.anatomical_structure Medicine business Motor learning motor learning Neuroscience Motor deterioration Gene Deletion 030217 neurology & neurosurgery |
| Zdroj: | eLife eLife, Vol 10 (2021) |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.64833 |
| Popis: | Rett syndrome is a devastating childhood neurological disorder caused by mutations in MECP2. Of the many symptoms, motor deterioration is a significant problem for patients. In mice, deleting Mecp2 from the cortex or basal ganglia causes motor dysfunction, hypoactivity, and tremor, which are abnormalities observed in patients. Little is known about the function of Mecp2 in the cerebellum, a brain region critical for motor function. Here we show that deleting Mecp2 from the cerebellum, but not from its neuronal subtypes, causes a delay in motor learning that is overcome by additional training. We observed irregular firing rates of Purkinje cells and altered heterochromatin architecture within the cerebellum of knockout mice. These findings demonstrate that the motor deficits present in Rett syndrome arise, in part, from cerebellar dysfunction. For Rett syndrome and other neurodevelopmental disorders, our results highlight the importance of understanding which brain regions contribute to disease phenotypes. |
| Databáze: | OpenAIRE |
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