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

2008 Fiscal Year Annual Research Report

• Project/Area Number: 18658105
• Research Institution: The University of Tokyo
• Principal Investigator: 眞鍋 昇 The University of Tokyo, 大学院・農学生命科学研究科, 教授 (80243070)
• 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

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。

Research Products

• [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
  • Journal Title: Reproduction in Domestic Animals 43 Pages: 268-272
  • Peer Reviewed
• [Journal Article] Regulation of granulosa cell apoptosis by death ligand-receptor signaling. (2008)
  • Author(s): Fuko Matsuda, Akihisa Maeda, Yuan Cheng, Takafumi, Sai, Hiroshi Gonda, Noboru Manabe
  • Journal Title: Animal Science Journal 79 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Physiological roles of inhibin in regulation of FSH secretion and follicular development during early pregnancy in goats. (2008)
  • Author(s): Mohamed MM Kandiel, Gen Watanabe, Junyou Li, Noboru Manabe, Abd El Salam I El Azap, Kazuyoshi Taya
  • Journal Title: Domestic Animals Endocrinology 35 Pages: 157-163
  • Peer Reviewed
• [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
  • Journal Title: The Journal of Reproduction and Devevelopment 54 Pages: 275-280
  • Peer Reviewed
• [Journal Article] cFLIP regulates death receptor-mediated apoptosis in an ovarian granulosa cell line by inhibiting procaspase-8 cleavage. (2008)
  • Author(s): Fuko Matsuda, Naoko Inoue, Yasufumi Goto, Akihisa Maeda, Yuan Chang, Kazuhiro Sakamaki, Noboru Manabe
  • Journal Title: The Journal of Reproduction and Devevelopment 54 Pages: 314-320
  • Peer Reviewed
• [Journal Article] Changes in expression and localization of X-linked inhibitor of apoptosis protein (XIAP) in follicular granulosa cells during atresia in porcine ovaries. (2008)
  • Author(s): Yuan Chang, Akihisa Maeda, Yasufumi Goto, Fuko Matsuda, Takashi Miyano, Noboru Manabe
  • Journal Title: The Journal of Reproduction and Devevelopment 54 Pages: 454-459
  • Peer Reviewed
• [Journal Article] Incorporation of β-amyloid protein through the bovine ileal epithelium before and after weaning : model for orally transmitted amyloidoses. (2008)
  • Author(s): Yasuhisa Ano, Hiroyuki Nakayama, Yasuke Sakai, Akikazu Sakudo, Maiko Endo, Shogo Ebisu, Jun-You Li, Koji uetsuka, Noboru Manabe
  • Journal Title: Microbiology and Immunolog 52 Pages: 429-434
  • Peer Reviewed
• [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
  • Journal Title: Okajimas Folia Anatomica Japonica 85 Pages: 73-77
  • Peer Reviewed
• [Journal Article] Establishment of an efficient enzyme-linked immunosorbent assay for the detection of Eperythrozoon sius antibody in swine. (2008)
  • Author(s): Shoufa Zhang, Yulin Ju, Lijun Jia, Susumu Kumagai, Junyou Li, Noboru Manabe
  • Journal Title: The Journal of Veterinary Medical Science 70 Pages: 1143-1145
  • Peer Reviewed
• [Presentation] ブタ黄体退行における抗アポトーシス因子とアポトーシス因子の役割 (2009)
  • Author(s): 高橋創、杉本美紀、奥田潔、李俊佑、眞鍋昇
  • Organizer: 第111回日本畜産学会
  • Place of Presentation: 藤沢市
  • Year and Date: 2009-03-27
• [Presentation] X-linked inhibitor of apoptosis protein (XIAP) regulaters apoptosis in follicular granulosa cells in porcine ovaries. (2008)
  • Author(s): Noboru Manabe, Junyou Li
  • Organizer: The 5^<th> Asian Reproductive Biotechnology Society Conference
  • Place of Presentation: 中国・雲南市
  • Year and Date: 2008-11-28
• [Presentation] The relation between concentrations of progesterone, estradiol and ovulation after PGF2alpha injection at varied day of after ovlation in Shiba-goat. (2008)
  • Author(s): Junyou Li, Noboru Manabe
  • Organizer: The 5^<th> Asian Reproductive Biotechnology Society Conference
  • Place of Presentation: 中国・雲南市
  • Year and Date: 2008-11-28
• [Presentation] Orally administrated ferulic acid metabolism in the rat, (2008)
  • Author(s): Hiroshi Gonda, Takuya Nakagami, Hiroyuki Hashimoto, Takuo Tsuno, Noboru Manabe
  • Organizer: The 2^<nd> International Symposium on Rice and Protection of Diseases
  • Place of Presentation: 和歌山市
  • Year and Date: 2008-10-20
• [Presentation] Interleukin-6 regulaters granulosa cell apoptosis during follicular atresia in porcine ovaries. (2008)
  • Author(s): Noboru Manabe
  • Organizer: The 113^<th> Animal Science Cogress of the Asian-Australasian Association of Animal Production Societies
  • Place of Presentation: ベトナム・ハノイ市
  • Year and Date: 2008-09-24
• [Presentation] XIAPはブタ顆粒層細胞においてアポトーシスを阻害する (2008)
  • Author(s): 程園、前田晃央、高橋創、眞鍋昇
  • Organizer: 第101回日本繁殖生物学会
  • Place of Presentation: 福岡市
  • Year and Date: 2008-09-19
• [Presentation] cFLIP regulated corpus lutea development during estrus cycle and pregnancy in rat. (2008)
  • Author(s): Kannika WONGPANIT, Akihisa MAEDA, Noboru MANABE
  • Organizer: 第101回日本繁殖生物学会
  • Place of Presentation: 福岡市
  • Year and Date: 2008-09-19
• [Presentation] ブタ黄体細胞における細胞内抗アポトーシス因子cFLIPに関する研究 (2008)
  • Author(s): 金花子、李俊佑、Kannika WONGPANIT、奥田潔、眞鍋昇
  • Organizer: 第101回日本繁殖生物学会
  • Place of Presentation: 福岡市
  • Year and Date: 2008-09-19
• [Presentation] 卵核胞顕微移植によるガラス化保存されたブタ発育完了および発育途中卵母細胞の減数分裂能の検討 (2008)
  • Author(s): 中川奨麻、前泊直樹、菊池和弘、永井卓、眞鍋昇
  • Organizer: 第101回日本繁殖生物学会
  • Place of Presentation: 福岡市
  • Year and Date: 2008-09-19
• [Presentation] PGF2alpha投与時期によるシバヤギ血中P4とE2濃度変化と排卵 (2008)
  • Author(s): 李俊佑、金花子、Kannika WONGPANIT、眞鍋昇
  • Organizer: 第101回日本繁殖生物学会
  • Place of Presentation: 福岡市
  • Year and Date: 2008-09-19
• [Presentation] How to assess the quality of mammalian oocytes as animal biotechnology resource: cFLIP is an adequate indicator. (2008)
  • Author(s): Noboru Manabe, Junyou Li
  • Organizer: Yanbian International Symposium on Strategies for the Development of Animal Science and Livestock Industry in China
  • Place of Presentation: 中国・延辺市
  • Year and Date: 2008-09-05
• [Presentation] Reproductive technology of dairy cow in Japan (2008)
  • Author(s): Junyou Li, Noboru Manabe
  • Organizer: Yanbian International Symposium on Strategies for the Development of Animal Science and Livestock Industry in China
  • Place of Presentation: 中国・延辺市
  • Year and Date: 2008-09-05
• [Presentation] Role of cell death liganh and receptor system on regulation of follicular atresia in pig ovaries. (2008)
  • Author(s): Noboru Manabe
  • Organizer: The 16^<th> International Congress on Animal Reproduction
  • Place of Presentation: ハンガリー・ブタベスト市
  • Year and Date: 2008-07-15
• [Presentation] Apoptosis in porcine granulosa cells during follicular atresia is regulated by anti-apoptotic cFLIP. (2008)
  • Author(s): Noboru Manabe, Fuko Minehata, Yasufumi Goto, Akihisa Maeda, Yuan Cheng, Naoko Inoue
  • Organizer: The 1^<st> World Congress on Reproductive Biology
  • Place of Presentation: アメリカ合衆国・コナ市
  • Year and Date: 2008-05-25
• [Presentation] Ex-vivo growth and maturation of oocytes in farm animals. (2008)
  • Author(s): Takashi Yano, Noboru Manabe
  • Organizer: The 1^<st> World Congress on Reproductive Biology
  • Place of Presentation: アメリカ合衆国・コナ市
  • Year and Date: 2008-05-25
• [Presentation] Abnormality of localization and expression of aquaporins in the kidneys of ICR-derived glomerulonephritis (ICGN) mice. (2008)
  • Author(s): Noboru Manabe, Toshiharu Mori, Yasufumi Goto, Sayuri Anann, Chinatsu Sakata, Tshihiro Lee, Kozue-Uchino
  • Organizer: Annual Meeting of the ICGN-mouse Reserch Society
  • Place of Presentation: 茨木市
  • Year and Date: 2008-04-20
• [Presentation] Reproductive characteristics of ICR-derived glomerulonephritis (ICGN) mice. (2008)
  • Author(s): Kozue-Uchino, Kyoko Sawada, Takanori Kunieda, Noboru Manabe
  • Organizer: Annual Meeting of the ICGN-mouse Reserch Society
  • Place of Presentation: 茨木市
  • Year and Date: 2008-04-20
• [Presentation] Localization of tissue transglutaminase in the kidneys of ICR-derived glomerulonephritis (ICGN) mice. (2008)
  • Author(s): Yohei Miyamoto, Akira Myoumoto, Mizuki Yamada-Yamaguchi, Kozue-Uchino, Noboru Manabe
  • Organizer: Annual Meeting of the ICGN-mouse Reserch Society
  • Place of Presentation: 茨木市
  • Year and Date: 2008-04-20
• [Presentation] ヤギcFLIP遺伝子のクローニングと卵胞顆粒層細胞における発現 (2008)
  • Author(s): 権田寛、眞鍋昇
  • Organizer: 第109回日本畜産学会
  • Place of Presentation: 水戸市
  • Year and Date: 2008-04-02
• [Book] Division, growth and differentiation of cells. In:Veterinary Embryology (2008)
  • Author(s): Noboru Manabe
  • Total Pages: 392
  • Publisher: Gakusoshya Pub. Co, Tokyo, Japan
• [Book] Female reproductive organs. In:Veterinary Histology 4^<th> edition. (2008)
  • Author(s): Noboru Manabe, Jyunpei Kimura
  • Total Pages: 344
  • Publisher: Gakusoshya Pub. Co, Tokyo, Japan
• [Book] Ooncyte growth and acquisition of meiotic competence. In:Gamete Biology:Emerging frontiers on fertility and contraceptive development. (2008)
  • Author(s): Takashi Miyano, Noboru Manabe
  • Total Pages: 545
  • Publisher: Nottingham University Press, Norringham, United Kingdom
• [Book] Color Atras of Veterinary Anatomy; Volume 1 and 2 (2008)
  • Author(s): Noboru Manabe
  • Total Pages: 837
  • Publisher: Chikusann-syuppann-Midori-shobo Co., Tokyo,Japan
• [Remarks]
  • URL: http://park.itc.u-tokyo.ac.jp/bokujo/