Establishment of TDP-43 C-terminal deficient mice using zinc finger nuclease and application to the model for amyotrophic lateral sclerosis
| Project/Area Number |
25461271
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kitasato University (2014-2015)
Niigata University (2013) |
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Principal Investigator |
SATO TOSHIYA 北里大学, 医学部, 教授 (90359703)
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| Co-Investigator(Kenkyū-buntansha) |
KODERA YOSHIO 北里大学, 理学部, 准教授 (60265733)
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| Co-Investigator(Renkei-kenkyūsha) |
ONODERA OSAMU 新潟大学, 脳研究所, 教授 (20303167)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ALS / TDP-43 / 疾患モデル / 脳神経疾患 / 発生・分化 |
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| Outline of Final Research Achievements |
To investigate the physiological functions of the C-terminal region (CTR) of TDP-43, we established eight lines of CTR deficient mice using zinc finger nuclease. Mutant TDP-43 mice carrying a deletion within 6 amino acids in the middle of CTR (A) appeared normal even in the homozygote, whereas homozygous mice carrying a large deletion of the N- (B; 262-348) or C-terminal (C; 345-414) half of CTR showed embryonic lethality. In the brains of heterozygous B or C mice, a comparable level of the truncated protein corresponding to the large deletion was observed only in B mice. The truncated TDP-43 was exclusively in the cytoplasm fraction, thus it could not show physiological function in the nucleus. These results show N-terminal half of CTR is essential for maintaining nuclear function of TDP-43, whereas C-terminal half of CTR is important for the protein stability.
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Report
(4 results)
Research Products
(11 results)
