Deleting Mecp2 from the cerebellum rather than its neuronal subtypes causes a delay in motor learning in mice.

Autor:	Achilly NP; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.; Program in Developmental Biology, Baylor College of Medicine, Houston, United States.; Medical Scientist Training Program, Baylor College of Medicine, Houston, United States., He LJ; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, United States.; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States., Kim OA; Department of Neuroscience, Baylor College of Medicine, Houston, United States., Ohmae S; Department of Neuroscience, Baylor College of Medicine, Houston, United States., Wojaczynski GJ; Department of Neuroscience, Baylor College of Medicine, Houston, United States., Lin T; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.; Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States., Sillitoe RV; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.; Program in Developmental Biology, Baylor College of Medicine, Houston, United States.; Department of Neuroscience, Baylor College of Medicine, Houston, United States.; Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States., Medina JF; Department of Neuroscience, Baylor College of Medicine, Houston, United States., Zoghbi HY; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.; Program in Developmental Biology, Baylor College of Medicine, Houston, United States.; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.; Department of Neuroscience, Baylor College of Medicine, Houston, United States.; Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States.; Department of Neurology, Baylor College of Medicine, Houston, United States.; Department of Pediatrics, Baylor College of Medicine, Houston, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Jan 26; Vol. 10. Date of Electronic Publication: 2021 Jan 26.
DOI:	10.7554/eLife.64833
Abstrakt:	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. Competing Interests: NA, LH, OK, SO, GW, TL, JM No competing interests declared, RS Reviewing Editor, eLife, HZ Senior editor, eLife (© 2021, Achilly et al.)
Databáze:	MEDLINE
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