2014 Fiscal Year Final Research Report
Analyses of regulatory mechanisms of TDP-43 level and risk factor of ALS
| Project/Area Number |
24300122
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Research Collaborator |
HARA Chikako 東京慈恵会医科大学, 医学部, 助教 (40528452)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | ALS / TDP-43 / RNA結合タンパク質 |
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| Outline of Final Research Achievements |
TDP-43 gene has been identified as a causative gene of amyotrophic lateral sclerosis (ALS) . Two types of mutant TDP-43 knock-in (mTDP-43 KI) mice with mutations in different sites of the gene were generated to investigate the biological effects of each mutation. Considerable phenotypes were observed in mTDP-43 KI mice: poor weight gain and loss of spinal motor neurons, which is related to ALS symptoms. By Exon Array and RT-PCR, defects of RNA metabolism following TDP-43 dysfunction were detected in the mononuclear cells from peripheral blood of KI mice. Furthermore, up-regulation of mutant TDP-43 was detected in astrocytes adjacent to motor neurons from KI mice. Our results, referencing TDP-43 mutations, will provide new insights into the pathophysiology of ALS.
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| Free Research Field |
分子神経化学
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