Analysis of mTOR signaling in central nervous systems

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06701
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: The University of Tokyo
• Principal Investigator: Kassai Hidetoshi 東京大学, 大学院医学系研究科(医学部), 准教授 (40403232)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: mTOR / トランスジェニックマウス / 小脳

Outline of Final Research Achievements

We aimed to examine mTOR functions in cerebellar Purkinje cells (PCs) by establishing a mouse model of chronically activated mTOR pathway in PCs. Using constitutively active mTOR, we established double transgenic mice line, in which active mTOR mutant is expressed specifically in PCs (L7-mTOR Tg mice). Immunohistochemical analysis showed that PCs of L7-mTOR Tg mice were remarkably hypertrophied and significantly decreased in their number at 4 weeks of age. Molecularly, L7-mTOR Tg PCs were immunopositive for cleaved caspase 3 and HIF-1alpha, suggesting that PC loss by mTORC1 activation may be caused by apoptotic cell death via hypoxic stress signaling. Behavioral analyses revealed that L7-mTOR Tg mice displayed impaired motor coordination, but normal social behavior. Together, these results indicate that mTORC1 signaling is essential for PC survival and cerebellar functions.

Free Research Field

分子遺伝学