Gene therapy against Rett syndrome and functional analysis of MeCP2, using blood-brain barrier-penetrating AAV vectors

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02521
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Gunma University
• Principal Investigator: HIRAI HIROKAZU 群馬大学, 大学院医学系研究科, 教授 (70291086)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 自閉症 / MeCP2 / AAV

Outline of Final Research Achievements

Rett syndrome and MeCP2 duplication syndrome, which are characterized by various manifestations such as autism and epilepsy, are caused by mutation of MeCP2 gene. MeCP2 is critical for brain development in both neurons and astrocytes. In this study, we examined which MeCP2 in neurons or in astrocytes is critical for brain function of mature mice. We found that overexpression of MeCP2 in astrocytes caused no abnormal phenotypes, while overexpression in neurons induced impaired social behavior. In addition, we succeeded to knockout MeCP2 gene from mature mouse cerebellar neurons.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

MeCP2はニューロンとアストロサイトの両方で、脳の発達に重要な役割を果たすことが知られている。しかし、MeCP2は成熟後も脳で発現し続けるが、成熟脳における役割はほとんど明らかになっていない。本研究で、成熟マウスのニューロンにMeCP2を過剰発現させると他のマウスにあまり関心を示さなくなった。すなわち、ニューロンに発現するMeCP2は他者とコミュニケーションをとる社会行動に重要な役割を果たすことが示唆された。