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1996 Fiscal Year Final Research Report Summary

Development of new technology for transgene methods in mice

Research Project

Project/Area Number 06558114
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section試験
Research Field Laboratory animal science
Research InstitutionNational Institute of Neuroscience, NCNP

Principal Investigator

NABESHIMA Yo-ichi  National Institute of neuroscience, Director, 神経研究遺伝子工学, 部長 (60108024)

Co-Investigator(Kenkyū-buntansha) FUJISAWA Atsuko  National Institute of neuroscience, Group Chief, 神経センター・神経研究所遺伝子工学, 室長 (60209038)
HANAOKA Kazunori  Kitazato Uni. Faculty of Science, Professor, 理学部, 教授 (40189577)
Project Period (FY) 1994 – 1996
KeywordsHomologous Recombination / ES cell / Cre-recombinase / loxP sequence / Premature aging / Insertion mutation
Research Abstract

Application of Cre-loxP system for gene engineering in mice.
To develop the technology required for tissue and stage restricted gene disruption in mice, we tried the application of Cre-loxP system and obtained following results. At first, we constructed the gene targeting vector which had three loxP sequences at just 5' and 3' ends of Neo-TK cassette (inserted at upstream of the target sequence) and at downstream of the target sequence. Then, homologous recombinant ES cells were isolated and the Neo-TK cassette was removed off by the expression of Cre-recombinase. These recombinant ES cells were injected into fertilized eggs to generate chimeric mice. The histological and functional analyzes of hetero and homozygous mutant mice are now in progress.
2) Isolation and analysis of premature aging mice.
We recently developed a unique short life mouse strain in which a single gene mutation caused a premature aging, including arteriosclerosis, osteoporosis, impaired spermatogenesis and oocyte maturation, soft tissue calcification, atrophy of thymus, pulmonary emphysema, degeneration of Purkinje cells, and impaired glucose metabolism.However, the mice did not show any abnormality in lipid metabolisms. We have isolated the causative gene from both mouse and human. Furthermore, the ectopic expression of the isolated gene successively rescued the mutant phenotypes. The gene has been found to be a novel one encoding a membrane protein and expressed mainly in kidney and brain. In human a secreted protein, in adition to membrane protein, is generated from same gene by alternative splicing mechanism.

  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Sekido R.,Murai K.,Funahasi J.,Kamachi Y.,Fujisawa-Sehara A.,Nabeshima Y.and Kondoh H.: "d-Crystallin enhancer binding protein dEFl is a repressor of E2-Box-mediated gene activation" Mol.Cell.Biol.14. 5692-5700 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuro-o M.,Hanaoka K.,Noguchi T.,Hiroi Y.,Fujimori Y.Takewaki S.,Hayasaka M.,Aikawa M.,Katoh H.: "Miyagishi A.,Nagai R.,Yazaki Y.,and Nabeshima Y.Overezpression of sodium-proton exchanger causes salt-sensitive blood pressure elevation in transgenic mice." Circulation Res. 76. 148-153 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirata J.,Nakagoshi H.,Nabeshima Y.and Matsuzaki F.: "Asymmetric segregation of the homeodomain protein Prospero during Drosophila development" Nature. 377. 627-630 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yagami-Hiromasa T.,Sato T.,Sato T.,Kurisaki T.,Kamijo K.,Nabeshima Y.and Fujisawa-Sehara A.: "A metalloproteasedisintegrin participating in myoblast fusion" Nature. 377. 652-656 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida S.,Fujisawa-Sehara A.,Arai K.and Nabeshima Y.: "Lysophosphatidic acid and bFGF control different modes in proliferating myoblasts." J.Cell Biol.132. 181-193 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hoshino M.,Suzuki E.,Nabeshima Y.and Hama C.: "hikaru genki protein secreted into synaptic clefts from an early stage of synapse formation in Drosophila" Development. 122. 589-597 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohbayashi T.,Schmidt E.E.,Makino Y.,Kishimoto T.,Nabeshima Y.,Muramatsu M.,and Tamura T.: "Promoter structure of the mouse TATA-binding protein(TBP)gene." B.B.R.C.225. 275-280 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sone M.,Hoshino M.,Suzuki E.,Saigo K.,Nabeshima Y.,and Hama C.: "Still life,a protein in synaptic tereminals of Drosophila homologous to GDP-GTP exchanger." Science. 275. 543-547 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "ジーンターゲッテイングと疾患解明・骨格筋の発生・分化" 羊土社. 45-57 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 黒尾誠、広井透雄、竹脇俊一、相川真範、永井良三、花岡和則、早坂美智子、鍋島陽一、野口毅、宮岸明、加藤祐久、矢崎義雄: "発生工学的技術を用いた新しい高血圧モデル動物の開発--Na+/H+逆輪送担体を過剰発現するトランスジェニックマウスの病態解析" 医薬ジャーナル. 30. (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "発生・分化と転写調節" 特集 遺伝子発現と転写因子 Mebio 11. 98. 212-216 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "相同組み換えを用いた遺伝子変異導入法" BIO Clinica 北隆館. 9. 201-205 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "第2世代の相同組み換え技術とその応用" BIO Clinica 北隆館. 9. 752-756 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "筋疾患、筋細胞研究のモデルマウス、マニュアル:疾患モデルマウス" Molecular Medicine 中山書店. 130-137 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "発生と分化" 日本臨床特別号 臨床分子生物学 日本臨床社. 83-90 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "筋発生の分子機構--MyoDファミリーの機能を中心として--" 蛋白質 核酸 酵素. 40. 101-113 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉田松生、鍋島陽一: "筋細胞をモデルとした増殖と分化の選択機構の解析 発生工学 特集 転写因子ネットワーク" 秀潤社. 172-175 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "HLHファミリー 用語ライブラリー「細胞内シグナル伝達」" 羊土社. 781-788 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "MyoDファミリー Bio Science 用語ライブラリー「転写因子」" 羊土社. 168-170 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "現代の生命科学シリーズ 丸山工作 監修 分担執筆" 講談社. (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "筋収縮蛋白遺伝子の構造と発現 筋肉病学 分担執筆" 南江堂. 339-350 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "筋疾患、筋発生研究のモデル動物の開発" 蛋白質、核酸、酵素 増刊号「トランスジェニック動物」. 2197-2203 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武田伸一,鍋島陽一: "筋ジストロフィー" 蛋白質、核酸、酵素 増刊号「遺伝子治療」. 40. 2765-2771 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 石井亜紀子、武田伸一、鍋島陽一: "筋細胞" 実験医学別冊「遺伝子治療の基礎技術」. 172-179 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "筋細胞分化の遺伝子制御ネットワーク" The Bone[硬組織細胞と分子発生生物学」. 10. 97-106 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "筋細胞分化の遺伝子制御ネットワーク" 蛋白質、核酸、酵素 増刊号「遺伝子機能と転写因子」. 41. 1008-1017 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "筋細胞分化における遺伝子の段階的活性化" 生体の科学 特集「細胞分化」. 47. 184-189 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鍋島陽一: "筋細胞の増殖因子 脳と神経科学シリーズ 1 「遺伝子異常からみた神経疾患」" メデイカル ビュウ. 36-44 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sekido R., Murai K., Funahashi J., Kamachi Y., Fujisawa-Sehara A., Nabeshima Y.and Kondoh H.: "delta-Crystallin enhancer binding protein deltaEF1 is a repressor of E2-Box-mediated gene activation." Mol. Cell. Biol.14. 5692-5700 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuro-o M., Hanaoka K., Noguchi T., Hiroi Y., Fujimori Y., Takewaki S., Hayasaka M., Aikawa M., Katoh H., Miyagishi A., Nagai R., Yazaki Y., and Nabeshima Y.: "Overezpression of sodium-proton exchanger causes salt-sensitive blood pressure elevation in transgenic mice." Circulation Res.76. 148-153 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirata J., Nakagoshi H., Nabeshima Y.and Matsuzaki F.: "Asymmetric segregation of the homeodomain protein Prospero during Drosophila development." Nature. 377. 627-630 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yagami-Hiromasa T., Sato T., Kurisaki T., Kamijo K., Nabeshima Y.and Fujisawa-Sehara A.: "A metalloprotease-disintegrin participating in myoblast fusion" Nature. 377. 652-656 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida S., Fujisawa-Sehara A., Arai K.and Nabeshima Y.: "Lysophosphatidic acid and bFGF control different modes in proliferating myoblasts." J.Cell Biol.132. 181-193 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hoshino M., Suzuki E., Nabeshima Y.and Hama C.: "hikaru genki protein secreted into synaptic clefts from an early stage of synapse formation in Drosophila." Developmant. 122. 589-597 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohbayashi T., Schmidt E.E., Makino Y., Kishimoto T., Nabeshima Y., Muramatsu M., and Tamura T.: "Promoter structure of the mouse TATA-binding protein (TBP) gene." Biochem. Biophys. Res. Comm.225. 275-280 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sone M., Hoshino M., Suzuki E., Saigo K., Nabeshima Y., and Hama C.: "Still life, a protein in synaptic tereminals of Drosophila homologous to GDP-GTP exchanger." Science. 275. 543-547 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida N.Yoshida S., Fujisawa-Sehara A., and Nabeshima Y.: "Variation of MyoD and myf-5, which precedes myogenin expression and irreversible commitment, specifies the differentiating and "Reserve Cells" upon myogenesis." J.Cell Biol.(Submitted).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyagoe Y., Terashima T., Nonaka I., Hanaoka K., Hayasaka M., Nabeshima Y., Arahata K., Takeda S.and Nabeshima Y.: "The laminin a2 chain is required for maturation of skeletal muscle and migration of neurons." (Submitted).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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