Elucidation of roles of precursor mRNA alternative splicing in obesity pathology

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09855
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Gunma University
• Principal Investigator: Satoh Tetsurou 群馬大学, 医学部附属病院, 非常勤講師 (40302484)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 選択的スプライシング / THRAP3 / 白色脂肪細胞 / 肝臓 / ノックアウト / マウス

Outline of Final Research Achievements

The physiological role of THRAP3, which functions as a transcription factor / splicing factor, in vivo is unknown. In this study, to analyze the role of THRAP3 in the pathology of obesity, we created white adipocyte- and liver-specific THRAP3 knockout (KO) mice. The number of births of organ-specific KO mice was lower than expected, and some KO mice were considered to lead to embryonic lethality. No clear pathological abnormalities were found in the KO mice that were successfully born, and there were no significant differences in food intake, body weight, and glucose tolerance under the standard diet or high-fat diet compared with the control. From now on, it is necessary to search for the cause of embryonic lethality, increase the number of individuals, and perform further analysis.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

mRNA選択的splicing (AS)は、単一遺伝子から複数の蛋白isoformが翻訳されて個の多様性を生み出す生体内機構であり、その異常は癌や神経変性疾患の原因となる。近年私達は転写共役因子Helz2 knock-out (KO)マウスが肥満に対して抵抗性になることを報告した。更にHelz2に結合する蛋白としてsplicing因子であるThrap3を同定し、Thrap3がHelz2と協調的に白色脂肪細胞分化を促進することも報告した。本研究では、私達が樹立した臓器特異的Thrap3 KOマウスを用いて、Thrap3の生体内機能解析を行い、AS異常が肥満症病態に及ぼす影響について検討した。