Frontier studies in development and cancer

2009 Fiscal Year Final Research Report

• Project/Area Number: 17012018
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kumamoto University
• Principal Investigator: YAMAMURA Kenichi Kumamoto University, 生命資源研究・支援センター, 教授 (90115197)
• Co-Investigator(Renkei-kenkyūsha): KAWAKAMI Minoru 熊本大学, 発生医学研究所, 助教 (40363527)
• Project Period (FY): 2005 – 2009
• Keywords: 遺伝子トラップ / Abhd2 / Spink3 / Atg5 / 条件的遺伝子破壊 / オートファジー

Research Abstract

We carried out gene trap mutagenesis using the exchangeable gene trap method and 800 gene trap clones with information of gene names and insertion sites were deposited to EGTC bank and database. The germ-line competent ES cell lines derived from the Japanese wild mouse, MSM/Ms, was established. We developed the exchangeable gene targeting method using Cre-mutant lox system. We demonstrated that the Abhd2 gene, the Skt gene, the Lgr4 gene, and the Spink3 gene are involved in migration of smooth muscle cells and differentiation of monocyte into macrophage, in tail vertebrate formation, development of epididymidis and gall bladder, and in inhibition of autophagy and cell proliferation through EGFR pathway, respectively.

Research Products

• [Journal Article] Serine protease inhibitor, Kazal type 1, promotes proliferation of pancreatic cancer cells through the epidermal growth factor receptor. (2009)
  • Author(s): Ozaki, N., Ohmuraya, M., Hirota, M., Ida, S., Wang, J., Takamori, H., Higashiyama, S., Baba, H., Yamamura, K.
  • Journal Title: Mol. Cancer Res 7巻 Pages: 1572-1581
• [Journal Article] Defective development of the gall bladder and cystic duct in Lgr4-hypomorphic mice. (2009)
  • Author(s): Yamashita, R., Takegawa, Y., Sakumoto, M., Nakahara, M., Kawazu, H., Hoshii, T., Araki, K., Yokouchi, Y., Yamamura, K.
  • Journal Title: Mechanism Dev 238巻 Pages: 993-1000
• [Journal Article] Establishment of germline-competent embryonic stem cell lines from the MSM/Ms strain. (2009)
  • Author(s): Araki, K., Takeda, T., Yoshiki, A., Obata, Y., Nakagata, N., Shiroishi, T., Moriwaki, K., Yamamura, K.
  • Journal Title: Mammal. Genome 20巻 Pages: 14-20
• [Journal Article] Involvement of autophagy in trypsinogen activation. (2008)
  • Author(s): Hashimoto, D., Ohmuraya, M., Hirota, M., Yamamoto, A., Suyama, K., Baba, H., Araki, K., Mizushima, N., Yamamura, K.
  • Journal Title: J. Cell Biol. 181巻 Pages: 1065-1072
• [Journal Article] Elevated expression of human・ABHD2 gene in mature macrophage in vulnerable plaques. Biochem. (2008)
  • Author(s): Miyata, K., Nakayama, M., Mizuta, S., Hokimoto, S., Sugamura, K., Oshima, S., Oike, Y., Sugiyama, S., Ogawa, H., Yamamura, K.
  • Journal Title: Biophys. Res. Commun. 365巻 Pages: 207-213
• [Journal Article] LGR4 regulates the postnatal development and integrity of male reproductive tracts in mice. (2007)
  • Author(s): Hoshii, T., Takeo, T., Nakagata, N., Takeya, M., Araki, K., Yamamura, K.
  • Journal Title: Biol. Reprod. 76巻 Pages: 303-313
• [Journal Article] Enhanced trypsin activity in pancreatic acinar cells deficient for serine protease inhibitor Kazal type 3. (2006)
  • Author(s): Ohmuraya, M., Hirota, M., Araki, K., Baba, H., Yamamura, K.
  • Journal Title: Pancreas 33巻 Pages: 104-106
• [Journal Article] A novel murine gene, Sickle tail (Skt), linked to the Danforth's short tail (Sd) locus, is required for normal development of the intervertebral disc. (2006)
  • Author(s): Semba, K., Araki, K., Li, Z., Matsumoto, K., Suzuki, M., Nakagata, N., Takagi, K., Takeya, M., Yoshinobu, K., Araki, M., Imai, K., Abe, K., Yamamura, K.
  • Journal Title: Genetics 172巻 Pages: 445-456
• [Journal Article] Autophagic cell death of pancreatic acinar cells in serine protease inhibitor Kazal Type 3 deficient mice. (2005)
  • Author(s): Ohmuraya, M., Hirota, M., Araki, M., Mizushima, N., Matsui, M., Mizumoto, T., Haruna, K., Kume, S., Takeya, M., Ogawa, M., Araki, K., Yamamura, K.
  • Journal Title: Gastroenterology 129巻 Pages: 696-705
• [Journal Article] Increase of smooth muscle cell migration and of intimal hyperplasia in mice lacking the abhydrolase domain containing 2 gene. (2005)
  • Author(s): Miyata, K, Oike, Y, Hoshii, T, Maekawa, H, Ogawa, H, Suda, T, Araki, K, Yamamura, K.
  • Journal Title: Biochem Biophys Res Commun 329巻 Pages: 296-304
  • Peer Reviewed
• [Presentation] MMS/Ms mouse as a tool for humanized mouse project in Japan (2009)
  • Author(s): Yamamura, K., Araki, K.
  • Organizer: Fourth meeting on Asian Mouse Mutagenesis and Resource Association
  • Place of Presentation: Kumamoto
  • Year and Date: 2009-12-17
• [Presentation] Pancreatic Acinar Cell Death In Spink3 Deficient Mice (2009)
  • Author(s): Yamamura, K.
  • Organizer: 40th Anniversary Joint Meeting of the American Pancreatic Association & Japan Pancreas Society
  • Place of Presentation: Hawaii
  • Year and Date: 2009-11-06
• [Presentation] ヒト疾患の遺伝学的解析のためのモデルマウス(シンポジウム) (2008)
  • Author(s): 山村研一
  • Organizer: 日本人類遺伝学会第53回大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-09-02
• [Presentation] ヒト疾患研究における動物モデルの有用性と世界の現状(教育講演2) (2007)
  • Author(s): 山村研一
  • Organizer: 第52回大会日本人類遺伝学会ゲ ノム解析から臨床応用へのロードマップ
  • Place of Presentation: 東京
  • Year and Date: 2007-09-14
• [Presentation] Exchangeable gene trap as a tool in the mouse knockout project(symposium), The 12th International Symposium for Mouse Genomics The BK21 International Symposium of Veterinary Science (2007)
  • Author(s): Ken-ichi Yamamura
  • Organizer: Seoul National University
  • Place of Presentation: Korea
  • Year and Date: 2007-05-15
• [Book] 最新医学(ES細胞研究の歴史, 増刊号) (2009)
  • Author(s): 山村研一
  • Total Pages: 497-505
• [Book] 再生医療(学問領域としての「発生医学」の曙光期-日本における発生工学の黎明と「発生医学」への展開) (2009)
  • Author(s): 山村研一
  • Total Pages: 394-400
• [Remarks]
  • URL: http://www.irda.kumamoto-u.ac.jp/
• [Patent(Industrial Property Rights)] トラップベクターおよびこれを用いた遺伝子トラップ法 (2010)
  • Inventor(s): 山村研一、荒木喜美
  • Industrial Property Rights Holder: 株式会社トランスジェニック
  • Industrial Property Number: 特許・EP1201759
  • Filing Date: 2010-03-10
• [Patent(Industrial Property Rights)] トラップベクターおよびこれを用いた遺伝子トラップ法
  • Inventor(s): 山村研一、荒木喜美
  • Industrial Property Rights Holder: 株式会社トランスジェニック
  • Industrial Property Number: 特許・US7312075