| Project/Area Number |
16K15522
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
Aoki Yoko 東北大学, 医学系研究科, 教授 (80332500)
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| Co-Investigator(Kenkyū-buntansha) |
松原 洋一 国立研究開発法人国立成育医療研究センター, 所長室, 研究所長 (00209602)
新堀 哲也 東北大学, 医学系研究科, 准教授 (40436134)
井上 晋一 東北大学, 医学系研究科, 助教 (70622091)
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| Research Collaborator |
OBA Daiju 東北大学, 大学院医学系研究科
NISHIYAMA Ayumi 東北大学, 大学院医学系研究科
UMEKI Ikumi 東北大学, 大学院医学系研究科
TAKAHARA Shingo 東北大学, 大学院医学系研究科
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | がん原遺伝子 / 代謝 / コステロ症候群 / 体重増加不良 / Costello症候群 / 遺伝学 / 心肥大 / 遺伝子 |
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| Outline of Final Research Achievements |
To examine the mechanisms of energy reprogramming by HRAS activation in vivo, we generated knock-in mice expressing a heterozygous Hras G12S mutation (HrasG12S/+ mice) as a mouse model of Costello syndrome. On a high-fat diet, HrasG12S/+ mice developed a lean phenotype with microvesicular hepatic steatosis, resulting in early death compared with wild-type mice. Under starvation conditions, hypoketosis and elevated blood levels of long-chain fatty acylcarnitines were observed, suggesting impaired mitochondrial fatty acid oxidation. Our findings suggest that the oncogenic Hras mutation modulates energy homeostasis in vivo.
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