| Project/Area Number |
18K15678
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | University of Miyazaki |
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Principal Investigator |
Ikeda Toshio 宮崎大学, 医学部, 准教授 (20423717)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 疾患モデル / 早発性脳症 / 運動障害 / 胎児致死 / 遺伝子改編マウス / チューブリン / 神経変性疾患 / 胎児医学 / 遺伝子改変マウス / 脊髄性筋萎縮症 |
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| Outline of Final Research Achievements |
We evaluated mice with a modified Tbcd gene (KI: point mutation KO: 13 base deletion). KI heterozygous mice and KO heterozygous mice were normal, and KO homozygous mice (KO-/-) were fetal lethal. We performed the following analyses as TBCD gene abnormality model mice of early-onset encephalopathy. 1) Fetal mice evaluations of KO-/-(2) Follow-up of one KI homo-mouse case in long-term survival.
(1) We analyzed more than dozens of fetuses around 9.5-12.5 days of fetal life. Unfortunately, only 2 cases of KO-/-were obtained, and it was difficult due to early fetal lethality. Although we changed the analysis methods, it was difficult to continue the study with reproducibility due to premature fetal death. (2) A KI homozygous mouse developed motor paralysis of the lower limbs after long-term survival for two years. Evaluation in adults is possible, and future experiments will mainly evaluate KI mice.
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| Academic Significance and Societal Importance of the Research Achievements |
当初計画したTbcd遺伝子を改編したマウスによる解析のうち、KOホモマウスの解析は病状による胎仔早発死で再現性ある研究継続は困難とわかり、期間内の論文報告にはいたらなかった。しかし、新たにKIホモマウスにおいて長期生存後下肢の運動障害が発現することがわかった。今後の新たな解析・研究の方向性が導かれた。今後KIホモマウスの運動機能解析や組織解析等がTBCD遺伝子異常による早発性脳症を解明しうる、将来の研究につながる知見を得た
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