Molecular mechanisms of the fetal left-right axis malformations induced by maternal hyperglycemia.
Project/Area Number |
18K07880
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
|
Research Institution | Kyushu University |
Principal Investigator |
|
Project Period (FY) |
2018-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 糖尿病母体 / 左右軸 / 心臓発生 / 高血糖 / 左右軸形成 / 糖尿病 / 体軸形成 / Nodalシグナル / Wntシグナル / マウス初期胚 / マウス胚 / 原始結節 |
Outline of Final Research Achievements |
The expression of Nodal and Cerl2 was decreased in the node of 8.0-day embryo exposed to high glucose concentration, and it was due to the reduction of active form of NOTCH (NICD) in the node. We focused on Wnt3a which is required for the expression of NOTCH around the node in 8.0-day embryo, and identified two enhancers, PSE1 and PSE2, for primitive streak specific expression of Wnt3a. We first introduced point mutation in Wnt3a PSE1 by CRISPR/Cas9 system, but there was no significant decrease in expression of Wnt3a in the pimitive streak, and the obtained homozygote pups were viable.
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Academic Significance and Societal Importance of the Research Achievements |
糖尿病は先天異常を引き起こすリスク要因であり、形態学的には妊娠7週までに糖尿病による先天異常が生じると考えられている。疫学調査によって糖尿病による胎児の左右形態異常が裏付けれており、実験的には糖尿病モデルマウスの胎児にヒトと同様の左右形態異常が発生することが報告されているが、その発生機序については未だ不明である。我々の研究成果は、妊娠糖尿病が左右軸関連の先天異常発生を引き起こす要因を特定することで、エビデンスに基づいた妊婦への血糖管理や栄養指導に役立てることが可能となる。
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Report
(6 results)
Research Products
(3 results)
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[Journal Article] Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation.2020
Author(s)
Tomoaki Koga, Fumiyuki Sasaki, Kazuko Saeki, Soken Tsuchiya, Toshiaki Okuno, Mai Ohba, Takako Ichiki, Satoshi Iwamoto, Hirotsugu Uzawa, Keiko Kitajima, Chikara Meno, Eri Nakamura, Norihiro Tada, Yoshinori Fukui, Junichi Kikuta, Masaru Ishii, Yukihiko Sugimoto, and Mitsuyoshi Nakao, Takehiko Yokomizo.
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Journal Title
Cellular & Molecular Immunology
Volume: 8
Issue: 6
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Sox17 expression in the endocardium precursor cells regulates the mouse heart development2019
Author(s)
Rie Saba, Keiko Kitajima, Yasuinori Shintani, Yoshiakira Kanai, Masami Kanai-Azuma, Chikara Meno, Rumiko Saga, Ken Suzuki, Shigeru Miyagawa, Yoshiki Sawa, Hideya Yamazaki, Kei Yamada, Kenta Yasuhiro
Organizer
日本分子生物学会
Related Report
Int'l Joint Research
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