The cause of PPARgamma1 exonC-specific knockout homozygous fetal death in homozygous mice
Project/Area Number |
17K09866
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | Saitama Medical University |
Principal Investigator |
Inoue Ikuo 埼玉医科大学, 医学部, 教授 (60232526)
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Co-Investigator(Kenkyū-buntansha) |
中野 貴成 埼玉医科大学, 医学部, 講師 (20406474)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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Keywords | PPARγ / 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 / ペルオキシソーム増殖因子活性化受容体 / PPARγ1 / PPARγ2 / PPARγ1プロモータ / 新規スプライシングバリアント / PPARγ1ノックアウトマウス / 胎盤巨細胞 / プロモータ / 脂肪誘導 / BMAL1 / CLOCK / 時計遺伝子 / SV129マウス / C57Blackマウス / DBP / E4BP4 / 脂質 |
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.
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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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Report
(4 results)
Research Products
(56 results)
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[Journal Article] Statin Intolerance Clinical Guide 20182020
Author(s)
Kajinami K, Tsukamoto K, Koba S, Inoue I, Yamakawa M, Suzuki S, Hamano T, Saito H, Saito Y, Masuda S, Nakayama T, Okamura T, Yamashita S, Kagawa T, Kaneyama J, Kuriyama A, Tanaka R, Hirata A: Statin Intolerance Clinical Guide Working Group
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 27
Issue: 4
Pages: 375-396
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2020-04-01
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Redox-dependent PPARγ/Tnpo1 complex formation enhances PPARγ signalling2020
Author(s)
Toshiaki Teratani, Kengo Tomita, Sachiko Toma-Fukai, Yutaro Nakamura, Toshimasa Itoh, Hikaru Shimizu, Yasunaga Shiraishi, Nao Sugihara, Masaaki Higashiyama, Takahiko Shimizu, Ikuo Inoue, Yasuhiro Takenaka, Ryota Hokari, Takeshi Adachi, Toshiyuki Shimizu, Soichiro Miura, Takanori Kanai
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Journal Title
Free Radical Biology and Medicine (in press)
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Effects of linagliptin monotherapy compared with voglibose on postprandial lipid profiles in Japanese patients with type 2 diabetes: Linagliptin Study of Effects on Postprandial blood glucose (L-STEP) sub-study 1.2018
Author(s)
Kurozumi A, Okada Y, Satoh H, Inoue I, Chimori H, Akita E, Shiraiwa T, Fujitani Y, Mita T, Gosho M, Watada H
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Journal Title
Endocrine Journal
Volume: (in press)
NAID
Related Report
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[Journal Article] Effects of the activations of three major hepatic Akt substrates on glucose metabolism in male mice.2017
Author(s)
Sakai G, Inoue I, Suzuki T, Sumita T, Inukai K, Katayama S, Awata T, Yamada T, Asano T, Katagiri H, Noda M, Shimada A, Ono H.
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Journal Title
Endocrinology
Volume: 158
Pages: 2659-2671
Related Report
Peer Reviewed / Open Access
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[Journal Article] Linagliptin versus Voglibose on Glucose Excursion in Japanese Patients with Type 2 Diabetes Mellitus: Effect of Linagliptin on Daily Glucose Excursion in Continuous Glucose Monitoring of Japanese Type 2 Diabetic Patients (L-CGM study): Randomized, Open-Label, 2-Arm Parallel Comparative Trial.2017
Author(s)
Satoh H, Ohira T, Moriya C, Inoue I, Kuribayashi S, Seino H, Hirai H, Hiyoshi T, Watada H.
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Journal Title
Diabates & Metabolism
Volume: 43
Pages: 550-553
Related Report
Peer Reviewed / Open Access
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