Metablic alterarion and growth control in congenital anomaly syndrome

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15522
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: Aoki Yoko 東北大学, 医学系研究科, 教授 (80332500)
• 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)
• 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
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: がん原遺伝子 / 代謝 / コステロ症候群

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.

Free Research Field

分子遺伝学