| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Outline of Final Research Achievements |
TDP-43 has been linked to the pathophysiology of frontotemporal lobar degeneration and amyotrophic lateral sclerosis (FTD/ALS). It is still open to debate whether TDP-43 neurotoxicity is caused by a novel toxic gain-of-function mechanism of the aggregates or by a loss of its normal function. Since TDP-43 is critical for embryonic development and fat metabolism, conventional knockout methods have failed to generate good models of TDP-43 “loss of function” model for FLD/ALS. To circumvent these problems, we developed the neuronal-specific, tamoxifen-inducible TDP-43 knockout mice. After ablation of TDP-43, mice exhibited behavioral abnormalities, cognitive dysfunction and rapid progressive motor paralysis associated with neuronal loss and massive gliosis, which resembles FTD/ALS phonotypes. This mouse model represents TDP-43 “loss of function” model for FTD/ALS. We propose that TDP-43 neurotoxicity is caused by a loss of its normal function.
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