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野生遺伝子およびヒトDNA導入によるモデル動物の総合的開発システムの基礎的研究

Research Project

Project/Area Number 03206103
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionCentral Institute for Experimental Animals

Principal Investigator

野村 達次  (財)実験動物中央研究所, 所長 (10072399)

Co-Investigator(Kenkyū-buntansha) 山村 研一  熊本大学, 医学部・附属遺伝医学研究施設, 教授 (90115197)
森脇 和郎  国立遺伝学研究所, 細胞遺伝研究部門, 教授 (50000229)
中西 重忠  京都大学, 医学部・免疫研究施設第2, 教授 (20089105)
豊田 裕  東京大学, 医科学研究所, 教授 (90050418)
勝木 元也  九州大学, 生体防御医学研究所, 教授 (20051732)
Project Period (FY) 1987 – 1992
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥21,700,000 (Direct Cost: ¥21,700,000)
Fiscal Year 1991: ¥21,700,000 (Direct Cost: ¥21,700,000)
Keywords生物機能モデル / ヒト疾患モデル / トランスジェニックマウス / 野生マウス / ラボラトリ-マウス / ジ-ンタ-ゲッティング / 遺伝子操作 / モデル動物
Research Abstract

本研究は,野生およびヒトDNAを中心とする外来遺伝子DNAをマウスをはじめとする実験動物個体に導入し,新しい生物機能モデルおよびヒト疾患モデルを開発し,確立することを目的としている。野生遺伝子を野生マウスからラボラトリ-マウスに交配によって導入した結果,高頻度に組換えによる突然変異体が出現することをつきとめ,この現象に関与する遺伝子領域が特定された。また,野生マウスのミトコンドリアの同定からラボラトリ-マウスの先祖の特定に道が開かれるなど遺伝学の基礎研究に重要な生物モデルが得られた。つぎに,ヒトDNAをはじめとする外来遺伝子DNAの導入により,多くの新しいモデル動物としてトランスジェニックマウウの系統が確立した。そのなかには,がん,免疫不全,神経系の異常,糖尿病などのヒト疾患モデルも含まれる。これらの研究を支えるための支援的研究開発として,マウス胚,配偶子の凍結保存法が確立した。また公募研究からは,ジ-ンタ-ゲッティングによって,標的遺伝子が欠損したマウス個体が得られるなど,本研究班において重点と考えた課題に大きな成果が得られた。
以上の研究は,森脇班,勝木班,野村班の3班が実践的に行なった成果である。しかし,これらの班は,それぞれが独自性を生かすとともに相互に技術と知識とを交換し,普及するための講習会を実施するなどが不可欠であった。本総括班は,これらの相互に関連する研究の運営にあたって,厳しく評価し,重点的に費用の支出を計った。その結果,現代のバイオサイエンスにとって重要な個体レベルでの遺伝子操作によるモデル動物の開発と確立に新しいシステムが確立しつつあるものと考えられる。

Report

(1 results)
  • 1991 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] Kagiyama N: "Microbiological monitoring program of the ICLAS Monitoring Center(Asia)" in Proceedings,the 14th Seminar on Science and Technology‐Laboratory Animals‐. 83-100 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Katoh H: "Genetic monitoring system in the ICLAS Coordinating Monitoring Center(Asia)" in Proceedings,the 14th Seminar on Science and Technology‐Laboratory Animals‐. 467-469 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kaneda N: "Tissue‐specific and high‐level expression of the human tyrosine hydroxylase gene in transgenic mice" Neuron. 6. 583-594 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nagatsu I: "Expression in brain sensory neurons of the transgene in transgenic mice carrying human tyrosine hydroxylase gene" Neuroscience Letters. 127. 91-95 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Fukamizu A: "Human renin in transgenic mouse kidney is localized to juxtaglomerular cells" Biochem J. 278. 601-603 (1991)

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      1991 Annual Research Report
  • [Publications] Maruo K: "Toxicity of anticancer agents,growth and chemosensitivity of human tumour xenografts in a segregating stock of AF nude mice" Laboratory Animals. 25. 342-347 (1991)

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      1991 Annual Research Report
  • [Publications] Ebashi S: "ExcitationーContraction coupling and the mechanism of muscle contraction" Rev Physiol. 53. 1-16 (1991)

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      1991 Annual Research Report
  • [Publications] Ando K.: "Chemically induced forectomach papillomas in transgenic mice carry mutant human cーHaーras transgenes" Cancer Res.

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      1991 Annual Research Report
  • [Publications] Saitoh S: "De novo production of alph_2ーmacroglobulin in cultured astroglia from rat brain" Mol Brain Res. 12. 155-161 (1992)

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      1991 Annual Research Report
  • [Publications] Ito M.: "Fate of haploid parthenogenetic cells in mouse chimeras during development" J Exp Zool. 257. 178-183 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takahashi S: "Expression of the human angiotensinogen gene in transgenic mice and transfected cells" Bilchem Biophys Res Commun. 180. 1103-1109 (1991)

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      1991 Annual Research Report
  • [Publications] Sugimoto K: "Mutations of the p53 gene in lymphoid leukemia" Blood. 77. 1153-1156 (1991)

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      1991 Annual Research Report
  • [Publications] Takeda S: "Expression of SV40ーlacZ gene in mouse preimplantataion sembryos after pronuclear microinjection" Mol Reprod Dev.

    • Related Report
      1991 Annual Research Report
  • [Publications] Masu M: "Sequence and ezpression of a metabotropic glutamate receptor" Nature. 349. 760-765 (1991)

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      1991 Annual Research Report
  • [Publications] lchikawa T: "Spontaneous development of autoimmune uveorentintis in nude mice following reconstitution with embryonic rat thymus" Clin Exp lmmunol. 86. 112-117 (1991)

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      1991 Annual Research Report
  • [Publications] Tada T: "Transforming growth factorーbetaーinduced inhibition of T cell function;Susceptibility difference in T cell of various phenotypes and functions and its relevanse to immunosuppression in the tumorーbearing state" J lmmunol. 146. 1077-1082 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shimizu J: "Evidence for the functional binding in vivo of tumor rejection antigens to antigen‐presenting cells in tumorーbearing hosts" J lmmunol. 146. 1708-1714 (1991)

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      1991 Annual Research Report
  • [Publications] Matsubara K: "The genome efforts in Japan as of 1991" Genomics.

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      1991 Annual Research Report
  • [Publications] Hirayama K: "Develoment and stabiliry of human faecal faecal flora in the intestine of ex‐germ‐free mice" Micrbial Ecology Health Disease. 4. 95-99 (1991)

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      1991 Annual Research Report
  • [Publications] Shiroishi T: "Genetic control of sexーdependent meiotic recombination in the major histocompatibility complex of the mouse" EMBO J. 10. 681-686 (1991)

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      1991 Annual Research Report
  • [Publications] Winking H: "Polymorphic HSRs in chromosome 1 of the two semispecies Mus musculus musculus and M.m.domesticus have a common origin in an ancestral population" Chromosoma. 100. 147-151 (1991)

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      1991 Annual Research Report
  • [Publications] Tanaka S: "Gene responsible for deficient activity of the beta subunit of C8,the eighth component of complement,is located on mouse chromo some 4" Immunogenetics. 33. 18-23 (1991)

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      1991 Annual Research Report
  • [Publications] Yamaguchi M: "Molecular cloning and structural analysis of mouse gene and pseudogenes for proliferating cell nuclear antigen" Nucleic Acids Res. 19. 2403-2410 (1991)

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      1991 Annual Research Report
  • [Publications] Inaguma Y: "Acquisition of two endogenous ecotropic murine leukemia viruses in distinct Asian wild mouse populations" J Virol. 65. 1796-1802 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Styrna J: "lnfluence of partial deletion of the Y chromosome on mouse sperm phenotype" J Reprod Fert. 92. 187-195 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Styrna J: "An increased level of sperm abnormalities in mice with a partial deletion of the Y chromosome" Genet Res Camb. 57. 195-199 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kawashima T: "A new haplotype of the betaーglobin gene complex,Hbb^<w1> in Chinese wild mouse" Jpn J Genet. 66. 491-500 (1991)

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      1991 Annual Research Report
  • [Publications] Koseki H: "Dominant expression of a distinctive V14^+ Tーcell antigen receptor alpha chain in mice" Proc Natl Acad Sci USA. 88. 7518-7522 (1991)

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      1991 Annual Research Report
  • [Publications] Morimoto J: "New murine mammary tumor cell lines" In Vitro Gell Dev Biol. 27A. 349-351 (1991)

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      1991 Annual Research Report
  • [Publications] Era T: "Differentiation of growth signal requirement of B lymphocyte precursor is directed by expression of immunoglobulin" EMBO J. 10. 337-342 (1991)

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      1991 Annual Research Report
  • [Publications] Yamada G: "Specific depletion of the Bーcell population induced by aberrant expression of human interferon regulatory factor 1 gene in transgenic mice" Proc Natl Acad Sci USA. 88. 532-536 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shimada T: "Correction of ornithine transcarbamylase(OTC)deficiency in spfーash mice by introduction of rat OTC gene" FEBS Lett. 279. 198-200 (1991)

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      1991 Annual Research Report
  • [Publications] Yi S: "Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin(Met30)gene:Pathologic similarity to human familial amyloidotic polyneuropathy,type 1" Amer J Pathol. 138. 403-412 (1991)

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      1991 Annual Research Report
  • [Publications] Tominaga A: "Transgenic mice expressing a B cell growth and differentiation factor gene(lnterleukin 5)develop eosinophilia and autoantibody production" J Exp Med.

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      1991 Annual Research Report
  • [Publications] Qi SL: "Rapid identification of transgenic mice with PCR amplification of DNA from ear punching" Method Mol Cell Biol. 2. 119-122 (1991)

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      1991 Annual Research Report
  • [Publications] Yamamura K: "Manipulating the mouse genome:New approaches for the dissection of mouse development" Develop Growth Differ. 32. 93-100 (1991)

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      1991 Annual Research Report
  • [Publications] Mineta T: "(BALB/c×C57BL/6)F_1 mice are tolerant to undetectable mi×ed haplotype Abeta^dA alpha^b and mi×ed isotype A beta^d Eα^d self class II molecule" lnt lmmunol. 3. 453-460 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nishimoto H: "lーEーrestricted monoclonal expansion of B lymphocytes in the thymus of NOD mouse" lnternatl lmmunol. 3. 839-842 (1991)

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      1991 Annual Research Report
  • [Publications] Tashiro F: "Role of serum amylido P component for systemic amyloidosis in transgenic mice carrying human mutant transthyretin gene" Gerontology. 37. 56-62 (1991)

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      1991 Annual Research Report
  • [Publications] Uno M: "Complete prevention of diabetes in transgenic NOD mice expressing l‐E molecules" lmmunol Letters. 31. 47-52 (1991)

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      1991 Annual Research Report
  • [Publications] Niwa H: "Efficient selection for highーexpression transfectants with a novel eukaryotic vector" Gene. 108. 193-200 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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