Elucidation of roles of precursor mRNA alternative splicing in obesity pathology
| Project/Area Number |
17K09855
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Gunma University |
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Principal Investigator |
Satoh Tetsurou 群馬大学, 医学部附属病院, 非常勤講師 (40302484)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| 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 / 白色脂肪 / コンディショナルノックアウト / 白色脂肪組織 / メタボリック症候群 / ノックアウトマウス |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(37 results)
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[Journal Article] Genetics of Congenital Isolated TSH Deficiency: Mutation Screening of the Known Causative Genes and a Literature Review.2019
Author(s)
Sugisawa C, Takamizawa T, Abe K, Hasegawa T, Shiga K, Sugawara H, Ohsugi K, Muroya K, Asakura Y, Adachi M, Daitsu T, Numakura C, Koike A, Tsubaki J, Kitsuda K, Matsuura N, Taniyama M, Ishii S, Satoh T, Yamada M, Narumi S.
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Journal Title
J Clin Endocrinol Metab.
Volume: 104
Issue: 12
Pages: 6229-6237
DOI
Related Report
Peer Reviewed
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[Journal Article] Transducin β-like 1, X-linked and nuclear receptor co-repressor cooperatively augment the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors2018
Author(s)
Takamizawa T, Satoh T, Miyamoto T, Nakajima Y, Ishizuka T, Tomaru T, Yoshino S, Katano-Toki A, Nishikido A, Sapkota S, Watanabe T, Okamura S, Ishida E, Horiguchi K, Matsumoto S, Ishii S, Ozawa A, Shibusawa N, Okada S, Yamada M
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Journal Title
Endocrine Journal
Volume: 65
Issue: 8
Pages: 805-813
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access
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[Journal Article] Usage of continuous glucose monitoring (CGM) for detecting an unrecognized hypoglycemia and management of glucocorticoid replacement therapy in adult patients with central hypoadrenalism2018
Author(s)
Watanabe T, Ozawa A, Ishii S, Tomaru T, Shibusawa N, Saito T, Yamada E, Horiguchi K, Nakajima Y, Matsumoto S, Yoshino S, Katano-Toki A, Hashimoto K, Mori M, Okada S, Satoh T, Yamada M
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Journal Title
Endocrine Journal
Volume: 65
Issue: 5
Pages: 547-556
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pituitary NR4A1 is negatively regulated by thyroid hormone receptor without direct binding of thyroid hormone receptors on the gene.2017
Author(s)
Okamura A, Nakajima Y, Shibusawa N, Horiguchi K, Matsumoto S, Yamada E, Tomaru T, Ishii S, Ozawa A, Ishizuka T, Hashimoto K, Okada S, Satoh T, Yamada M
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Journal Title
Mol Cell Endocrine
Volume: 461
Pages: 32-42
DOI
Related Report
Peer Reviewed
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[Journal Article] Continuous transient high level of glucose exposure differentially increases coronary artery endotherial cell proliferation and human colon cancer cell proliferation.2017
Author(s)
Shimoda Y, Tagaya Y, Saito T, Yamada E, Osaki A, Nakajima Y, Ozawa A, Satoh T, Okada J, Okada S, Yamada M
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Journal Title
Cell J
Volume: 19
Pages: 106-112
Related Report
Peer Reviewed / Open Access
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