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KAKEN_25293345seika.pdf
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Title |
Title |
着床前期胚における「ゲノムの若返り」機構の解明
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Kana |
チャクショウ ゼンキハイ ニ オケル 「ゲノム ノ ワカガエリ」 キコウ ノ カイメイ
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Chakusho zenkihai ni okeru "genomu no wakagaeri" kiko no kaimei
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Molecular mechanisms of genomic rejuvenation during preimplantation development
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浜谷, 敏生
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ハマタニ, トシオ
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Romanization |
Hamatani, Toshio
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Affiliation |
慶應義塾大学・医学部・講師
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Research team head
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科研費研究者番号 : 60265882
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阿久津, 英憲
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アクツ, ヒデノリ
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Romanization |
Akutsu, Hidenori
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国立成育医療研究センター・生殖・細胞医療研究部・部長
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Research team member
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科研費研究者番号 : 50347225
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秦, 健一郎
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ハタ, ケンイチロウ
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Hata, Kenichiro
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国立成育医療研究センター・周産期病態研究部・部長
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Research team member
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科研費研究者番号 : 60360335
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津村, 秀樹
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ツムラ, ヒデキ
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Tsumura, Hideki
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国立成育医療研究センター・実験動物管理室・室長
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Research team member
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科研費研究者番号 : 20180052
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梅澤, 明弘
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ウメザワ, アキヒロ
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Umezawa, Akihiro
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国立成育医療研究センター・生殖・細胞医療研究部・部長
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Research team member
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科研費研究者番号 : 70213486
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2016
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科学研究費補助金研究成果報告書
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2015
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Abstract |
着床前期胚特異的新規遺伝子についてノックアウトマウス(KO)を作成し機能解析を行った。Kzpi(KRAB-zinc finger)のKOでは有意な産仔数の減少を認めた。Kzpi欠失ES細胞ではimprinted genesの発現異常, アレル特異的メチル化領域(DMR)の低メチル化が認められた。Kzpiは初期胚の脱メチル化に抗しDMRメチル化を維持すると考えられたが, 長期継代後は産仔数の減少もDMRメチル化の低下も消失した。Zfpi(SCAN-zf)のKOではQ-bandで多数の不完全断裂部位を認めた。Zfpi欠失ES細胞は奇形腫形成実験で三胚葉への分化を認めたが, 一部で胎児性癌が形成された。
This study found novel mouse genes (e.g. Kzpi encoding KRAB zinc-finger and Zfpi encoding SCAN-zinc finger) exclusively and zygotically expressed in preimplantation embryos and ES cells. Kzpi-deficient mice showed smaller litter sizes. Interestingly, most imprinted genes were down regulated and the methylation levels of differentially methylated regions (DMRs) were decreased in homozygous ES cells. Kzpi was thus suggested to maintain DMRs against genome-wide demethylation in preimplantation embryos. However, transgenerational phenotypic attenuation of Kzpi-deficient mice was observed: normal methylation patterns of DMRs in Kzpi-deficient blastocyst and ES cells. Zfpi-deficient mice did not show any phenotype, but karyotype analysis revealed chromosomal gaps. Kzpi-deficient ES cells generated a teratoma composed of all the three-germ layer, but gave rise to embryonal carcinoma.
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研究種目 : 基盤研究(B)(一般)
研究期間 : 2013~2015
課題番号 : 25293345
研究分野 : 医歯薬学
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