Neuro-pathological mechanism caused by impaired DNA damage response signaling
| Project/Area Number |
18H02624
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
Miyamoto Tatsuo 広島大学, 原爆放射線医科学研究所, 准教授 (40452627)
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| Co-Investigator(Kenkyū-buntansha) |
阿久津 シルビア夏子 (AkutsuSilviaNatsuko) 広島大学, 原爆放射線医科学研究所, 助教 (10822299)
松浦 伸也 広島大学, 原爆放射線医科学研究所, 教授 (90274133)
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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 |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Keywords | DNA修復欠損症 / DNA修復遺伝子欠損症 / ゲノム編集技術 / DNA損傷修復欠損症 / DNA修復遺伝子 / ゲノム編集 / 疾患モデル / DNA損傷修復 / 遺伝子改変動物 |
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| Outline of Final Research Achievements |
Germline mutations of the MRE11 gene, which encodes a DNA double-strand breakage repair enzyme MRE11 nuclease, cause neurodegeneration or microcephaly. Here we attempted to generate the MRE11 p.A47V mutation (ataxia-type)-homozygous mice and MRE11 c.658A>C splicing mutation (microcephaly type) . Unfortunately, the MRE11 c.658A>C splicing mutation homozygote did not any neurological phenotypes. In contrast, the MRE11 p.A47V mutation homozygotes showed a mild ataxia, suggesting these animals might be useful as a neurodegenerative disease model.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で作製したMRE11 A47Vミスセンス変異ホモ接合マウスは、神経変性疾患研究にとって有用なモデルマウスとして活用できる。また、本マウスの雄は生殖能力を有しているが、雌は不妊であった。本研究の予期せぬ成果として、MRE11の生殖細胞形成における寄与に性差があることが示されたと同時に、MRE11 A47Vミスセンス変異ホモ接合マウスは、生殖研究における新たな疾患モデルとして有用であることが示された。
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] Space radiation biology for “Living in Space”2020
Author(s)
Furukawa S, Nagamatsu A, Nenoi M, Fujimori A, Kakinuma S, Katsube T, Wang B, Tsuruoka C, Shirai T, Nakamura AJ, Sakaue-Sawano A, Miyawaki A, Harada H, Kobayashi M, Kobayashi J, Kunieda T, Funayama T, Suzuki M, Miyamoto T, Hidema J, Yoshida Y, Takahashi A.
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Journal Title
BioMed Res Int.
Volume: 2020
Pages: 4703286-4703286
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer2020
Author(s)
Lin Y, Nakatochi M, Hosono Y, Ito H, Kamatani Y, Inoko A, Sakamoto H, Kinoshita F, Kobayashi Y, Ishii H, Yamaji T,et al.
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Journal Title
Nature Communications
Volume: 11
Issue: 1
Pages: 3175-3175
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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