Characterization of ALS-Associated FUS Mutations using iPSCs and mouse models.

Research Project

Project/Area Number	24890228
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Neurology
Research Institution	Keio University
Principal Investigator	YAGI TAKUYA 慶應義塾大学, 医学部, 助教 (30528740)
Project Period (FY)	2012-08-31 – 2014-03-31
Project Status	Completed (Fiscal Year 2013)
Budget Amount *help	¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000) Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	筋萎縮性側索硬化症 / 遺伝子改変マウス / iPS細胞
Research Abstract	1. We generated iPSCs from fibroblasts obtained immediately postmortem from centenarian donors who were extremely healthy until an advanced age. The series of iPSCs would be useful in neurodegeneration and longevity research and as valid super-controls for use in studies of various late-onset diseases. 2. We generated transgenic mutant FUS mice under the control of thy-1 promoter who express mutant FUS protein ( C-terminal region deleted protein) particularly in the central nervous system. Motor phenotype evaluation showed no significant motor dysfunction through 50 weeks follow-up. Immunohistochemical study showed nuclear transport impairment, resulting in cytoplasmic accumulation of FUS protein. This finding is compatible with in vitro studies.