細胞死阻害因子の遺伝子導入による卵巣内潜在的卵母細胞を救命する異種移植法の開発
| Project/Area Number |
18658105
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| Research Category |
Grant-in-Aid for Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied animal science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
眞鍋 昇 The University of Tokyo, 大学院・農学生命科学研究科, 教授 (80243070)
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| Project Period (FY) |
2006 – 2008
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| Project Status |
Completed (Fiscal Year 2008)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2008: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2007: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | アポートシス / 卵巣 / 卵胞 / 顆粒層細胞 / アポートシス阻害因子 / 卵巣内潜在的卵母細胞 / カスパーゼ系 / 細胞死リガンド・受容体系 / 哺乳類 / 選択的死減 / アポトーシス / 細胞死受容体 / カスパーゼ / アポトーシス阻害因子 / 選択的死滅 |
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| Research Abstract |
成熟した雌家畜の卵巣内には胎児期にディプロテン期で減数分裂を休止した卵母細胞が50万個前後含まれ、性周期毎に卵母細胞は卵胞とともに発育・成熟して排卵に至る。この課程で、最終的に排卵にいたるものの100倍以上もの卵胞が発達を開始するが、殆どが選択的に死滅して1%以下が排卵に至る。この卵胞・卵子の選択的死滅はより優秀で強靭な子孫を残す戦略として重要であるが、分子制御機構は未解明である。本研究は、家畜の卵巣において繰り返される卵胞の選択的死滅を制御している分子機構を解明し、これをもとに卵巣組織の凍結保存法を開発して、卵巣内潜在的卵母細胞を救命することで雌性遺伝子資源の保存を実現する技術を確立することを目指している。昨年度に続いて今年度も卵胞に発現している細胞死受容体系の同定をすすめ、細胞死受容体を介するアポトーシスシグナルの細胞内伝達系の分子機構を精査した。その結果卵胞顆粒層細胞が閉鎖に支配的に関わり、これは細胞内アポトーシスシグナルがミトコンドリアを介して伝達するII型アポトーシス細胞であることを明らかにした。さらに細胞内でアポトーシスシグナル伝達を阻害している新規な阻害因子cFLIPとXIAP(家畜の遺伝子とアミノ酸配列を決定した)を突き止め、免疫不全マウスの腎に異種移植した家畜の未成熟卵胞を含む卵巣組織細片を対象にしてこの阻害因子のin vivo遺伝子導入やiRNA-発現阻害処理を施して、卵胞・卵母細胞の生死を制御して救命する人為的手を開発した。
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Report
(3 results)
Research Products
(89 results)
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[Journal Article] Role of cell death ligand and receptor system on regulation of follicular atresia in pig ovaries.2008
Author(s)
Noboru Manabe, Fuko Minehata, Yasufumi Goto, Akihisa Maeda, Yuan Cheng, Shoma Nakagawa, Naoko Inoue, Kannika Wongpanit, Hua-Zi Jin, Hiroshi Gonda, Jun-You Li
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Journal Title
Reproduction in Domestic Animals 43
Pages: 268-272
Related Report
Peer Reviewed
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[Journal Article] Molecular cloning of a porcine (Sus scrofa) apoptosis inhibitory ligand, Netrin-1, and its receptor, p53RDL1.2008
Author(s)
Akihisa Maeda, Fuko Matsuda, Yasufumi Goto, Yuan Cheng, Hiroshi Goto, Naoko Inoue, Shoma Nakagawa, Noboru Manabe
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Journal Title
The Journal of Reproduction and Devevelopment 54
Pages: 275-280
NAID
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Peer Reviewed
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[Journal Article] Ratio of peripheral nervous tissues in tongues, skeletal muscles and intestines in cows.2008
Author(s)
Xiao-Bo Zhu, Shogo Matoba, Kenshiro Hara, Yasuhisa Ano, shinichi Kobayashi, Naoki Tsunekawa, Yoshiakira Kanai, Noboru Manabe, Takashi Onodera, Masamichi Kurohmaru
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Journal Title
Okajimas Folia Anatomica Japonica 85
Pages: 73-77
NAID
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Peer Reviewed
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[Journal Article] Cell death ligand and receptor dependent regulatory mecha nisms of follicule selection in porcine ovaries2007
Author(s)
Noboru Manabe, Akihisa Maeda, Yasufumi Goto, Fuko Minehata, Naoko Inoue, Yuan Cheng, Huazi Jin, Kannika Wongpanit, Shoma Nakagawa, Jun-You Li, Takashi Miyano, Kazuhiro Sakamaki
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Journal Title
Morphology 2
Pages: 28-40
Related Report
Peer Reviewed
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[Journal Article] Mitochondrion-dependent intra-cellular apoptosis signaling pathway is dominant in follicular granulosa cell of pig ovaries2007
Author(s)
Yasufumi Goto, Toshikatu Matsui, Naoko Inoue, Fuko Minehata, Akihisa Maeda, Yuan Cheng, Huazi Jin, Kannika Wongpanit, Shoma Nakagawa, Jun-You Li, Noboru Manabe
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Journal Title
Morphology 2
Pages: 61-66
Related Report
Peer Reviewed
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[Journal Article] The initiator caspase, caspase-10beta, and the BH-3-only molecule, Bid, demonstrate evolutionary conservation in Xenopus of their pro-apoptotic activities in the extrinsic and intrinsic pathways.2006
Author(s)
Katsuya Kominami, Chiyo Takagi, Tomoko Kurata, Atsushi Kitayama, Masami Nozaki, Tatsuya Sawasaki, Keisuke Kuida, Yaeta Endo, Noboru Manabe, Naoto Ueno, Kazuhiro Sakamaki
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Journal Title
Genes to Cells 11・5
Pages: 701-717
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[Journal Article] Changes in expression of anti-apoptotic protein, cFLIP, in granulose cells during follicular atresia in porcine ovaries.2006
Author(s)
Noboru Manabe, Fuko Matsuda-Minehata, Yasufumi Goto, Akihisa Maeda, Yuan Cheng, Takafumi Sai, Miyuki Kohori, Maiko Endo, Junyou Li
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Journal Title
European journal of Cellular and Molecular Physiopathology 44・1
Pages: 120-124
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[Journal Article] Production of infectious hepatitis C virus particles in three-dimensional cultures of the cell line carrying the genome-length dicistronic viral RNA of genotype 1b.2006
Author(s)
Kyoko Murakami, Koji Ishii, Yousuke Ishihara, Sayaka Yoshizaki, Keiko Tanaka, Yasufumi Gotoh, Hideki Aizaki, Michinori Kohara, Hiroshi Yoshioka, Yuichi Mori, Noboru Manabe, Ikuo Shoji, Tetsutaro Sata, Ralf Bartenschlager, Yoshiharu Matsuura, Tatsuo Miyamura, Tetsuro Suzuki
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Journal Title
Virology 351・3
Pages: 381-392
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[Presentation] Regulation of follicular atresia by cell death ligand and receptor system2007
Author(s)
Noboru Manabe, Fuko Matsuda-Minehata, Yasufumi Goto, Akihisa Maeda, Yuan Cheng, Hiroshi Gonda, kannika Wongpanit, Huazi Jin, Junyou Li, Kazuhiro Sakamaki, Takashi Miyano
Organizer
The 4th Asian Reproductive Biotechnology Conference
Place of Presentation
Singapore, Singapor
Year and Date
2007-11-25
Related Report
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[Presentation] Follicle atresia and its regulation: Granulosa cell, a type II apoptotic cell, regulates follicular atresia in porcine ovarie2007
Author(s)
Noboru Manabe, Fuko Matsuda-Minehata, Yasufumi Goto, Akihisa Maeda, Yuan Cheng, Fanzu Jin, Junyou Li, Kannika Wongpanit
Organizer
The 2nd Conference on Asian Association of Veterinary Anatomists
Place of Presentation
Bangkon,Thailand
Year and Date
2007-09-13
Related Report
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[Presentation] Localization of anti-apoptosis protein, cflip, in mammalian ovaries2007
Author(s)
Hiroshi Gonda, Kannika Wongpanit, Akihisa Maeda, Yuan Cheng, Junyou Li, Fuko Matsuda-Minehata, Yasufumi Goto, Noboru Manabe
Organizer
The 2nd Conference on Asian Association of Veterinary Anatomists
Place of Presentation
Bangkon, Thailand
Year and Date
2007-09-13
Related Report
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