Mechanism of high-fat diet-induced fatty liver in mouse model reproducing gene-gene interaction.
Project/Area Number |
18K05532
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 38050:Food sciences-related
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Research Institution | Nagoya University |
Principal Investigator |
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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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 脂肪肝 / 遺伝解析 / 異所性脂肪蓄積 / Iah1 / ゲノム編集 / 脂肪組織 / ノックアウトマウス / QTL / 脂質代謝 / 疾患感受性遺伝子座 / マウスモデル |
Outline of Final Research Achievements |
NAFLD is one of multiple factorial diseases caused by the interaction between genetic factor and environmental factor. Genetic analysis of high-fat induced fatty liver model SMXA-5 mice, derived from fatty liver-resistant parental strains, revealed that Iah1 was a candidate gene for fatty liver. I constructed two Iah1 knockout mice (A/J-12SM Iah1 KO and B6N-Iah1 KO). These Iah1 knockout mice did not show the accumulation of triglycerides in liver. This study showed that Iah1 gene was not involved in the development of high-fat induced-fatty liver.
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Academic Significance and Societal Importance of the Research Achievements |
Fl1saの候補遺伝子として選抜したIah1の機能については酵母以外での報告は存在せず、マウス個体を用いたIah1の機能解析を行なった初めての研究である。多遺伝子で発症する疾患の遺伝子同定の手法としてCRISPR/Cas9システムを利用することにより、動物個体において候補遺伝子とその他の遺伝子群との相互作用を再現することができた。また、肝外組織である脂肪組織において遺伝子発現変動が見られ遺伝子はIah1の直接的な影響ではなく、全身の代謝変化による2次的なものであると考えられ、細胞系での遺伝子の機能解析では得られない変化を動物個体での解析が提示することを示すものである。
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Report
(4 results)
Research Products
(3 results)
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[Journal Article] Ablation of Iah1, a candidate gene for diet-induced fatty liver, does not affect liver lipid accumulation in mice.2020
Author(s)
Masuya, T., Suzuki, M., Tsujimura, J., Kanamori, S., Miyasaka, Y., Ohno, T., Murai, A., Horio, F. and Kobayashi, M.
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Journal Title
PLOS ONE
Volume: 15
Issue: 5
Pages: e0233087-e0233087
DOI
Related Report
Peer Reviewed / Open Access
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