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2019 Fiscal Year Final Research Report

The cause of PPARgamma1 exonC-specific knockout homozygous fetal death in homozygous mice

Research Project

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Project/Area Number 17K09866
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionSaitama Medical University

Principal Investigator

Inoue Ikuo  埼玉医科大学, 医学部, 教授 (60232526)

Co-Investigator(Kenkyū-buntansha) 中野 貴成  埼玉医科大学, 医学部, 講師 (20406474)
Project Period (FY) 2017-04-01 – 2020-03-31
KeywordsPPARγ / PPARγスプライシングバリアント / 胎盤 / 栄養膜巨大細胞 / 核内倍化 / 血小板巨核細胞
Outline of Final Research Achievements

In the murine placentas, peroxisome proliferator-activated receptor (PPAR) γ1, a nuclear receptor, becomes abundant at the late stage of pregnancy (E15-E16), but the functional roles are still elusive because PPARγ-knockout embryos die early (E10). We have generated mice disrupted only for Pparγ1, one of the two major mRNA splicing variants for PPARγ1. Pparγ1-knockout embryos developed normally until 15.5 dpc, but the growth retarded thereafter, and did not survive. At 15.5 dpc, in the wildtype placentas, intense PPARγ-immunostainings were detected in sinusoidal trophoblast giant cells (sTGCs), a cell lineage that coordinates the maternal blood microcirculation in the labyrinth, while were absent in the knockouts. Although Pparγ1-knockout placentas were normal in morphology, we observed severely dilated maternal blood sinuses in the labyrinth.

Free Research Field

内分泌代謝

Academic Significance and Societal Importance of the Research Achievements

PPARγ蛋白翻訳領域遺伝子完全KOマウスは胎生11.5週以降完全致死であることが報告されて以来(Barak Y, et al. Mol Cell.4:585-95,1999)、その機序を解明する報告はないが、我々が樹立したマウスは胎生15週までの胎仔を検討できることが学術的に独自性がある。胎生11.5週はヒト胎児21週に相当し、胎生11.5週以降15週までの胎仔のPPARγ1の機能を解析でき、また、これらを救済し、レスキューできれば、高血糖を有する妊婦が先天奇形および流産の頻度が増加することは臨床的にも明らかで、今後ヒトにも応用でき、本研究が新奇で独自的かつ生産的で創造性のある研究となる。

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Published: 2021-02-19  

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