Identification and functional analyses of proteins which are involved in the sterility and sperm production in testis

• Project/Area Number: 18390441
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: HARA Takahiko Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 副参事研究員 (80280949)
• Co-Investigator(Kenkyū-buntansha): KIYONO Mari 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 研究員 (60376621)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥2,880,000); Fiscal Year 2008: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2007: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2006: ¥5,200,000 (Direct Cost: ¥5,200,000)
• Keywords: 精巣 / 精子 / 精原細胞 / セルトリ細胞 / サイクリンD2 / リポカリン2

Research Abstract

精原細胞から分泌されたサイトカインは、隣接して存在するセルトリ細胞のNF-κB経路を活性化して、抗菌物質リポカリン2をコードする遺伝子の転写を高める。これが精巣を細菌感染から防御する仕組みであることを証明した。次に、精子数に影響を与える膜タンパク質S76の機能を解明するために、組織特異的な遺伝子破壊を可能とさせるS76-floxedマウス系統を新たに作出した。最後に、繊毛タンパク質CMG-1、およびRNAヘリカーゼDDX1が精原細胞の増殖分化に働く遺伝子群の転写を正に調節する、という新事実を見出した。

Research Products

• [Journal Article] DDX1 is required for testicular tumorigenesis, partially through the transcriptional activation of 12p stem cell genes. (2009)
  • Author(s): K. Tanaka, S. Okamoto, Y. Ishikawa, H. Tamura, and T. Hara.
  • Journal Title: Oncogene, advance online publication April 27
  • Peer Reviewed
• [Journal Article] Hematopoiesis-dependent expression of CD44 in murine hepatic progenitor cells. (2009)
  • Author(s): S. Ohata, M. Nawa, T. Kasama, T. Yamasaki, K. Sawanoboria, S. Hata, T. Nakamura, Y. Asaoka, T. Watanabe, H. Okamoto, T. Hara, S. Terai, I. Sakaida, T. Katada, and H. Nishina.
  • Journal Title: Biochem. Biophys. Res. Commun. 379 Pages: 817-823
  • Peer Reviewed
• [Journal Article] DDX1 is required for testicular tumorigenesis, partially through the transcriptional activation of 12p stem cell genes (2009)
  • Author(s): K. Tanaka, S. Okamoto, Y. Ishikawa, H. Tamura, T. Hara
  • Journal Title: Oncogene (In press)
  • Peer Reviewed
• [Journal Article] Hematopoiesis-dependent expression of CD44 in murine hepatic progenitor cells (2009)
  • Author(s): S. Ohata, M. Nawa, 8 authors, T. Hara, S. Terai, I. Sakaida, T. Katada, H. Nishina
  • Journal Title: Biochem. Biophys. Res. Commun. 379 Pages: 817-823
  • Peer Reviewed
• [Journal Article] Acceleration of chronic myeloproliferation by enforced expression of Meis1 or Meis3 in Icsbp-deficient bone marrow cells. (2008)
  • Author(s): T. Hara, M. Schwieger, R. Kazama, S. Okamoto, K. Minehata, M. Ziegler, J. Lohler, and C. Stocking.
  • Journal Title: Oncogene 27 Pages: 3865-3869
  • Peer Reviewed
• [Journal Article] Acceleration of chronic myeloproliferation by enforced expression of Meis1 or Meis3 in Icsbp-deficient bone marrow cells (2008)
  • Author(s): T. Hara, M. Schwieger, R. Kazama, S. Okamoto, K. Minehata, M. Ziegler, J. Lohler, C. Stocking
  • Journal Title: Oncogene 27 Pages: 3865-3869
  • Peer Reviewed
• [Journal Article] Acceleration of chronic myeloproliferation by enforced expression of Meisl or Meis3 in Icsbp-deficient bone marrow cells. (2008)
  • Author(s): T. Hara, M. Schwieger, et. al.
  • Journal Title: Oncogene (in press)
  • Peer Reviewed
• [Journal Article] Mitochondrial bottleneck occurs without reduction of mtDNA content in mouse female germ cells. (2007)
  • Author(s): L. Cao, H. Shitara, T. Horii, Y. Nagao, H. Imai, K. Abe, T. Hara, J. Hayashi, and H. Yonekawa.
  • Journal Title: Nat. Genet. 39 Pages: 386-390
  • Peer Reviewed
• [Journal Article] Mitochondrial bottleneck occurs without reduction of mtDNA content in mouse female germ cells. (2007)
  • Author(s): L. Cao, H. Shitara, et. al.
  • Journal Title: Nature Genetics 39 Pages: 386-390
  • Peer Reviewed
• [Journal Article] ヒトES細胞は上胚盤葉由来幹細胞EpiSCsに相当する (2007)
  • Author(s): 原 孝彦
  • Journal Title: 実験医学 25 Pages: 2166-2167
• [Journal Article] Mitochondrial bottleneck occurs without reduction of mtDNA content in mouse female germ cells (2007)
  • Author(s): L.Cao, H.Shitara, (4 authors), T.Hara, J.Hayashi, H.Yonekawa
  • Journal Title: Nature Genetics 39 Pages: 386-390
• [Journal Article] Crucial role of the small GTPase ARF6 in hepatic cord formation during liver development. (2006)
  • Author(s): T. Suzuki, Y. Kanai, T. Hara, J. Sasaki, T. Sasaki, M. Kohara, T. Maehama, C. Taya, H. Shitara, H. Yonekawa, M. A. Frohman, T. Yokozeki, and Y. Kanaho.
  • Journal Title: Mol. Cell Biol. 26 Pages: 6149-6156
• [Journal Article] Capillary morphogenesis gene (CMG)-1 is among the genes differentially expressed in mouse male germ line stem cells and embryonic stem cells. (2006)
  • Author(s): R. Fujino, Y. Ishikawa, K. Tanaka, M. Kanatsu-Shinohara, K. Tamura, H. Kogo, T. Shinohara and T. Hara.
  • Journal Title: Mol. Reprod. Dev. 73 Pages: 955-966
  • Peer Reviewed
• [Journal Article] Spermatogonial cell-mediated activation of an IκBζ-independent NF-кB pathway in Sertoli cells induces transcription of the lipocalin-2 gene. (2006)
  • Author(s): R. Fujino, K. Tanaka, M. Morimatsu, K. Tamura, H. Kogo, and T. Hara.
  • Journal Title: Mol. Endocrinol. 20 Pages: 904-915
  • Peer Reviewed
• [Journal Article] Spermatogonial cell-mediated activation of an IκBζ-independent NF-κB pathway in Sertoli cells induces transcription of the lipocalin-2 gene (2006)
  • Author(s): R.Fujino, K.Tanaka, (3 authors), T.Hara
  • Journal Title: Molecular Endocrinology 20 Pages: 904-915
• [Journal Article] Capillary morphogenesis gene (CMG)-1 is among the genes differentially expressed in mouse male germ line stem cells and embryonic stem cells (2006)
  • Author(s): R.Fujino, Y.Ishikawa, (5 authors), T.Hara
  • Journal Title: Molecular Reproduction and Development 72 Pages: 955-966
• [Journal Article] Crucial role of the small GTPase ARF6 in hepatic cord formation during liver development (2006)
  • Author(s): T.Suzuki, Y.Kanai, T.Hara, (9 authors), Y.Kanaho
  • Journal Title: Molecular and Cellular Biology 26 Pages: 6149-6156
• [Presentation] DDX1遺伝子の過剰発現が精巣腫瘍形成を促進する (2008)
  • Author(s): 田中貴代子, 原孝彦
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] CMG-1は精母細胞のCyclin-D2および接着関連遺伝子の転写を制御する (2008)
  • Author(s): 大林謙一郎, 田中貴代子, 藤野隆介, 田村和広, 原孝彦
  • Organizer: 第6回幹細胞シンポジウム
  • Place of Presentation: 東京
• [Presentation] 精巣腫瘍形成におけるDDX1の役割 (2008)
  • Author(s): 田中貴代子, 原孝彦
  • Organizer: 第6回幹細胞シンポジウム
  • Place of Presentation: 東京
• [Presentation] Ddx1遺伝子の精巣形成過程における発現と機能解析 (2007)
  • Author(s): 大林謙一郎、田中貴代子、藤野隆介、田村和広、向後博司、原孝彦
  • Organizer: 第30回日本分子生物学会年会BMB2007
  • Place of Presentation: 横浜
• [Presentation] Pre-leukemic amplification of granulocytes by enforced expression of Meis1 or Meis3 in hematopoietic stem cells of ICSBP-deficient mice. (2007)
  • Author(s): T. Hara, M. Schwieger, R. Kazama, S. Okamoto, and C. Stocking.
  • Organizer: 5th Annual Meeting of International Society for Stem Cell Research (ISSCR)
  • Place of Presentation: Cairns, Australia
• [Presentation] Meis1/3遺伝子はICSBP欠損マウスの顆粒球分化を促進する (2007)
  • Author(s): 原孝彦、Maike Schwieger、風間律子、岡本士毅、Carol Stocking
  • Organizer: 第5回幹細胞シンポジウム
  • Place of Presentation: 淡路島
• [Presentation] Ddx1遺伝子の精巣形成過程における発現と機能解析 (2007)
  • Author(s): 田中 貴代子、中山 由紀、原 孝彦
  • Organizer: 第30回日本分子生物学会年会-BMB2007
  • Place of Presentation: 横浜
• [Presentation] Physiological function of the small G protein ARF6 in hepatic cord formation and liver development. (2006)
  • Author(s): T. Suzuki, Y. Kanai,Y, T. Hara, J. Sasaki, T. Sasaki, M. Kohara, T. Maehama, T. Yokozeki, and Y. Kanaho.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: Kyoto
  • Year and Date: 2006-06-18
• [Presentation] A spermatogonial stem cell-derived factor induces the transcription of lipocalin-2/24p3 gene in Sertoli cells by an IкBκζ-independent NF-κB pathway. (2006)
  • Author(s): T. Hara, R. Fujino, K. Tanaka, M. Morimatsu, K. Tamura, and H. Kogo.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: Kyoto
• [Remarks]
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