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(In Japanese)変異マウスを用いた発癌制御遺伝子の単離・同定

Research report code R000000126
Posted date Sep 30, 2002
Researchers
  • (In Japanese)野田 哲生
Affiliation
  • (In Japanese)東北大学大学院医学系研究科 細胞生物学講座
Research organization
  • (In Japanese)(財)癌研究会癌研究所
  • (In Japanese)東北大学医学部
Report name (In Japanese)変異マウスを用いた発癌制御遺伝子の単離・同定
Technology summary (In Japanese)ヒト発癌の新たな予防や治療法の開発を目的として,マウスを用いての遺伝学的手法を駆使することにより,その発癌過程を正に負に制御している遺伝子群の単離・同定を行ない,発癌の分子機構の解明を行なっている。フォワード・ジェネティクスの手法では,ヒト発癌モデルマウスであるAPC変異マウスを用い,これと野生マウス由来の近交系マウスとの交配実験により,消化管腫瘍の発生を大きく抑制する機能を有する遺伝子座を数カ所同定し,遺伝子の単離・同定を目指して,コンジェニックマウスの作成を行なった。リバース・ジェネティックスの手法では,発癌機構の解明を目的として,APC遺伝子の不活化が生体内で上皮細胞を癌化させる分子機構を詳細に解析するため,各種組織特異的にCre組換え酵素を発現するトランスジェニックマウスを樹立し,コンディショナル・ターゲティング法による解析を行なった。これによりAPC遺伝子の不活化により生じる変化を詳細に解析可能となった。
Research field
  • Proteins and peptides in general
  • Enzyme in general
  • Genetic variation
  • Animal biochemistry
  • Chemistry, biochemistry and pathology of tumors (=neoplasms)
Published papers related (In Japanese)(1)Y. Doi, M. Itoh, S. Yonemura, S. Ishihara, H. Takano and T. Noda, S. Tsukita and S. Tsukita. (1999) Normal development of mice and unimpaired cell adhesion/fell motility/action-based cytoskeleton without compensatory up-regulation of Ezrin or Radixin in Moesin gene knockout. J. Biol. Chem., 274(4): 2315-2321.
(2)Y. Yoshihara, T. Mizuno, M. Nakahira, M. Kawasaki, Y. Watanabe, H. Kagamiyama, K. Jishage, O. Ueda, H. Suzuki, K. Tabuchi, K. Sawamoto, H. Okano, T. Noda and K. Mori. (1999) A genetic approach to visualization Neurotechnique of multisynaptic neural pathways using pant lectin transgene. Neuron, 22: 33-41.
(3)T. Kobayashi, O. Minowa, J. Kuno, H. Mitani, O. Hino and T. Noda. (1999) Renal carcinogenesis, hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice. Cancer. Res., 59: 1206-1211.
(4)M. Nishi, H. Takeshima, T. Houtani, K. Nakagawara, T. Noda and T. Sugimoto. (1999) RhoN, a novel small GTP-binding protein expressed predominantly in neurons and hepatic stellate cells. Mol. Brain. Res., 67: 74-81.
(5)A. Orimo, N. Tominaga, M. Suzuki, T. Kawakami, J. Kuno, M. Sato, O. Minowa, S. Inoue, S. Kato, T. Noda and M. Muramatsu. (1999) Successful germ-line transmission of chimeras generated by coculture aggregation with J1 ES cells and eight-cell embryos. Anal. Biochem., 269 (1): 204-207.
(6)I. Saito, K. Haruta, M. Shimuta, H. Inoue, H. Sakurai, K. Yamada, N. Ishimaru, H. Higashiyama, T. Sumida, H. Ishida, T. Suda, T. Noda, Y. Hayashi and K. Tsubota. (1999) Fas ligand-mediated exocrinopathy rersembling Sjogren's syndrome in mice transgenic for IL-10. J. Immunol., 162: 2488-2494.
(7)Y. Maeno, S. Moroi, H. Nagashima, T. Noda, H. Shiozaki, M. Monden, S. Tsukita and A. Nagafuchi. (1999) α-Catenin deficient F9 cells differenciate into signet ring cells. Am J Pathol., 154(5): 1323-1327.
(8)O. Minowa, K. Ikeda, Y. Sugitani, T. Oshima, S. Nakai, Y. Katori, M. Suzuki, M. Furukawa, T. Kawase, Y. Zheng, M. Ogura, Y. Asada, K. Watanabe, H. Yamanaka, S. Gotoh, M. Nishi-Takeshima, T. Sugimoto, T. Kikuchi, T. Takasaka, and T. Noda (1999) Altered cochlear fibrocytes in a moue model of DFN3 nonsyndromic deafness. Science, 285: 1408-1411.
(9)K. Miyasaka, H. Shinozaki, S. Suzuki, Y. Sato, S. Kanai, M. Masuda, A. Jimi, A. Nagata, T. Matsui, T. Noda, A. Kono and A. Funakoshi (1999) Disruption of cholecystokinin (CCK)-B receptor gene did not modify bile or pancreatic secretion or pancreatic growth: A study in CCK-B receptor gene knockout mice. Pancreas, 19(2): 114-118.
(10)M. Nishi, S. Komazaki. N. Kurebayashi, Y. Ogawa, T. Noda, M. Iino and H. Takeshima (1999) Abnormal features in skeletal muscle from mice lacking mitsugumin 29. J. Cell Biol., 147(7): 1473-1480.
(11)A. Orimo, S. Inoue, O. Minowa, N. Tominaga, Y. Tomioka, M. Sato, J. Kuno, H. Hiroi, Y. Shimizu, M. Suzuki, T. Noda and M. Muramatsu. (1999) Underdeveloped uterus and reduced estrogen responsiveness in mice with disruption of the estrogen-responsive finger protein (efp) gene, which is a direct target of estrogen receptor α (ER α). Proc. Natl. Acad. Sci. USA., 96 (21): 12027-12032.
(12)K. Murata, N. Ishii, H. Takano, S. Miura, LC. Ndhlovu, M. Nose, T. Noda, and K. Sugamura (2000) Impairment of antigen-presenting cell function in mice lacking expression of OX40 ligand. J. Exp. Med., 191(2): 365-374.
(13)H. Kawate, R. Itoh, K. Sakumi, Y. Nakabeppu, T. Tsuzuki, F. Ide, T. Ishikawa, T. Noda, H. Nawata and M. Sekiguchi (2000) A defect in a single allele of the Mlh1 gene causes dissociation of the killing and tumorigenic actions of an alkylating carcinogen in methyltransferase-deficient mice. Carcinogenesis, 21(2): 301-305.
(14)H. Beppu, M. Kawabata, T. Hamamoto, A. Chytil, O. Minowa, T. Noda and K. Miyazono (2000) BMP Type II receptor is required for gastrulation and early development of mouse embryos. Developmental Biology, 221: 249-258.
(15)O. Minowa, T. Arai, M. Hirano, Y. Monden, S. Nakai, M. Fukuda, M. Itoh, H. Takano, Y.Hippo, H. Aburatani, K. Masumura, T. Nohmi, S. Nishimura and T. Noda. (2000)
Mmh/Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice. Proc. Natl. Acad. Sci. USA, 97(8):4156-4161.
(16)H. Akazawa, I. Komuro, Y. Sugitani, Y. Yazaki, R. Nagai and T. Noda. (2000) Targeted disruption of the homeobox transcription factor Bapx1 results in lethal skeletal dysplasia with asplenia and gastroduodenal malformation. Genes to Cells, 5:499-513.
Research project
  • Core Research for Evolutional Science and Technology;Genetic Programming
Information research report
  • (In Japanese)野田 哲生. 生命活動のプログラム 変異マウスを用いた発癌制御遺伝子の単離・同定. 戦略的基礎研究推進事業 平成11年度 研究年報.科学技術振興事業団, 2000. p.102 - 106.

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