1991 Fiscal Year Annual Research Report

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 Institution	Central 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)
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。

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)
[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)
[Publications] Kaneda N: "Tissue‐specific and high‐level expression of the human tyrosine hydroxylase gene in transgenic mice" Neuron. 6. 583-594 (1991)
[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)
[Publications] Fukamizu A: "Human renin in transgenic mouse kidney is localized to juxtaglomerular cells" Biochem J. 278. 601-603 (1991)
[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)
[Publications] Ebashi S: "ExcitationーContraction coupling and the mechanism of muscle contraction" Rev Physiol. 53. 1-16 (1991)
[Publications] Ando K.: "Chemically induced forectomach papillomas in transgenic mice carry mutant human cーHaーras transgenes" Cancer Res.
[Publications] Saitoh S: "De novo production of alph_2ーmacroglobulin in cultured astroglia from rat brain" Mol Brain Res. 12. 155-161 (1992)
[Publications] Ito M.: "Fate of haploid parthenogenetic cells in mouse chimeras during development" J Exp Zool. 257. 178-183 (1991)
[Publications] Takahashi S: "Expression of the human angiotensinogen gene in transgenic mice and transfected cells" Bilchem Biophys Res Commun. 180. 1103-1109 (1991)
[Publications] Sugimoto K: "Mutations of the p53 gene in lymphoid leukemia" Blood. 77. 1153-1156 (1991)
[Publications] Takeda S: "Expression of SV40ーlacZ gene in mouse preimplantataion sembryos after pronuclear microinjection" Mol Reprod Dev.
[Publications] Masu M: "Sequence and ezpression of a metabotropic glutamate receptor" Nature. 349. 760-765 (1991)
[Publications] lchikawa T: "Spontaneous development of autoimmune uveorentintis in nude mice following reconstitution with embryonic rat thymus" Clin Exp lmmunol. 86. 112-117 (1991)
[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)
[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)
[Publications] Matsubara K: "The genome efforts in Japan as of 1991" Genomics.
[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)
[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)
[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)
[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)
[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)
[Publications] Inaguma Y: "Acquisition of two endogenous ecotropic murine leukemia viruses in distinct Asian wild mouse populations" J Virol. 65. 1796-1802 (1991)
[Publications] Styrna J: "lnfluence of partial deletion of the Y chromosome on mouse sperm phenotype" J Reprod Fert. 92. 187-195 (1991)
[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)
[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)
[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)
[Publications] Morimoto J: "New murine mammary tumor cell lines" In Vitro Gell Dev Biol. 27A. 349-351 (1991)
[Publications] Era T: "Differentiation of growth signal requirement of B lymphocyte precursor is directed by expression of immunoglobulin" EMBO J. 10. 337-342 (1991)
[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)
[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)
[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)
[Publications] Tominaga A: "Transgenic mice expressing a B cell growth and differentiation factor gene(lnterleukin 5)develop eosinophilia and autoantibody production" J Exp Med.
[Publications] Qi SL: "Rapid identification of transgenic mice with PCR amplification of DNA from ear punching" Method Mol Cell Biol. 2. 119-122 (1991)
[Publications] Yamamura K: "Manipulating the mouse genome:New approaches for the dissection of mouse development" Develop Growth Differ. 32. 93-100 (1991)
[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)
[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)
[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)
[Publications] Uno M: "Complete prevention of diabetes in transgenic NOD mice expressing l‐E molecules" lmmunol Letters. 31. 47-52 (1991)
[Publications] Niwa H: "Efficient selection for highーexpression transfectants with a novel eukaryotic vector" Gene. 108. 193-200 (1991)

1991 Fiscal Year Annual Research Report

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

Principal Investigator

野村 達次 (財)実験動物中央研究所, 所長 (10072399)

Research Products

[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)

[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)

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

[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)

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

[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)

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

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

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

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

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

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

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

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

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

[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)

[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)

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

[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)

[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)

[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)

[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)

[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)

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

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

[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)

[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)

[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)

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

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

[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)

[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)

[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)

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

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

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

[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)

[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)

[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)

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

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

野村達次 (財)実験動物中央研究所, 所長 (10072399)