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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 04206103
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, 付属遺伝発生医学研究施設, 教授 (90115197)
森脇 和郎  国立遺伝学研究所, 教授 (50000229)
中西 重忠  京都大学, 大学院・医学研究所, 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 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 1993: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1992: ¥21,000,000 (Direct Cost: ¥21,000,000)
Keywords遺伝子工学 / 発生工学 / ヒト疾患モデル / 生物機能モデル / 野生遺伝子導入動物 / DNA導入動物 / 体外受精 / 凍結保存
Research Abstract

動物実験は基礎および応用生物学にとって不可欠な研究手段である。とくに、最近では現代のバイオサイエンスの急速な発展を支える基礎として、研究目的に即した実験動物の開発が重要となってきた。この緊急の課題を遂行するためには、野生動物の遺伝子資源の利用および新しい技術による遺伝子操作モデル動物の開発と、それらの特性の研究および実用化システムの確立が必要となった。そこで昭和62年度から遺伝子工学と発生工学を駆使してヒト疾患モデルおよび生物機能モデルの作成を目的とする本研究が発足した。
本研究は、昭和62年度から平成4年度にかけて、総括班のもとで野生遺伝子導入動物班,DNA導入動物班,系統化班の3班および公募研究を総合的に運営した結果、当初の目的をほぼ達成することができた。さまざまなヒト疾患モデルマウスや生物機能モデルマウスが開発され、その遺伝子の特徴や疾患の発症をマウスによって研究できることが確認された。また体外受精,凍結保存,卵巣移殖などの発生工学技術が確立し、それにより大量の同一遺伝子をもつマウスを計画的に生産し、必要に応じて実験に給することができるようになった。
本年度は、これら、6年間の研究期間の成果を取りまとめ、また6年間の活動を記録した研究成果報告書を作成した。また、「大学と科学」公開シンポジウム『遺伝子から生命を探る-遺伝子導入動物研究の展開-』において、成果を一般に広く報告した。

Report

(2 results)
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] Nonaka M,Moriwaki K: "Molecular cloning of the b subunit of mouse coagulation factor XIII and assignment of the gene to chromosome 1:close evolutionary relationship to complement factor H" Genomics. 15. 535-542 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nass S J,Moriwaki K: "Mapping of the Mod‐1 locus on mouse chromosome 9" Mammalian Genome. 4. 333-337 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Wallin J,Moriwaki K: "A new pax gene,Pax‐9,maps to mouse chromosome 12" Mammalian Genome. 4. 354-358 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hayashi T,Moriwaki K: "A variant family of mouse minor satellite located on the centromeric region of chromosome 2" Genomics. 17. 490-492 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshiki A,Moriwaki K: "Histological studies on male sterility of hybrids between laboratory and wild mouse strains" Dev Growth Differ. 35. 271-281 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Obata Y,Moriwaki K: "The structure,function and evolution of mouse TL genes,nonclassical class I genes of the major histocompatibility complex" Proc Natl Acad Sci USA. in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Akiyama M,Katsuki M: "Lymphocyte infiltration of the skin in transgenic mice carrying the human interleukin‐2 gene" Arch Dermatol Res. 285. 379-384 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hayashizaki Y,Katsuki K: "Restriction landmark genomic scanning method and its various applications" Electrophoresis. 14. 251-258 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takaori K,Katsuki M: "Biochemical characterisics of human renin expressed in transgenic mice" Clin Sci. 84. 21-29 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shibata H,Moriwaki K: "Genetic mapping of mice endogenously imprinted loci systematically detected by restriction landmark genomic scanning(RLGS)" Mammalian Genome. in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Miyado K,Katsuki M: "Isolation of a yeast cDNA clone that encodes a noval transmembrane portein having a c‐terminal highly basic region" Biochem Biophys Res Commun. in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Nishiyori A,Yamamura K: "Detemination of tissue specificity of the enhancer by combinatorial oparation of tissue‐enriched transcription factors:Both HNF‐4 and C/EBP beta are required for liver‐specific activity of the omithine transcarbamylase enhancer" J Biol Chem. 269. 1323-1331 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shiroishi T,Moriwaki K: "Hotspots of meiotic recombination in the mouse major histocompatibility complex" Genetica. 88. 187-196 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshino M,Moriwaki K: "No dosage effect of recombinational hotspots in the mouse MHC" Immunogenetics. in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Kurihara Y,Moriwaki K: "Chromosome locations of Ag‐NORs and ribosomal DNA clusters in laboratory strains of mouse" Mammalian Genome. in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Suzuki H,Moriwaki K: "Sequences and evolutionary analysis of mouse 55 rDNAs" Mol Biol Evol. in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsuda Y,Moriwaki K: "Chromosomal mapping of mouse 5S rRNA genes by direct R‐banding fluorescence in situ hybridization" Cytogenet Cell Genet. in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Hayashizaki Y,Katsuki M: "Identification an imprinted U2af binding protein related sequence on mouse chromosome 11 using RLGS method" Nature Genetics. 6. 33-40 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Niwa H,Yamamura K: "An efficient gene‐trap method using poly A trap vectors and characterization of gene‐trap events" J Biochem. 113. 343-349 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakata K,Yamamura K: "Osteoarthritis associated with mild chondrodysplasia in transgenic mice expressing alpha1(IX)collagen chains with a central deletion" Proc Natl Acad Sci USA. 90. 2870-2874 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sakurada M,Yamamura K: "Relation between glucose‐stimulated insulin secretion and intracelluar calcium accumulation studied with a superfusion system of a glucose‐responsive pancreatic beta‐cell line MIN6" Endocrinology. 132. 2659-2665 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Miyazaki T,Yamamura K: "The role of macrophages in antigen presentation and T cell tolerance" Int Immunol. 5. 1023-1033 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yamamura K: "Transgenic mouse model for human genetic diseases" Mol Reprod Dev. 36. 248-250 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nishiyama T,Yamamura K: "Expression of the tyrosine‐kinase deficient human insulin receptor in transgenic mice" Gene. in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Obata Y,Moriwaki K: "Genetics in wild micc;its application to biomedical research(eds Moriwaki K,Shiroishi T,Yonekawa H)" Japan Scientific Societies Press,in Press,

    • Related Report
      1993 Annual Research Report
  • [Publications] Nomura T: "Poliovirus Attenuation:Molecular Mechanisms and Practical Aspects(eds Brown,F,Lewis BP)" Dev Biol Stand Basel Karger, 187 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kobayashi,K: "Gemetic alteration of catecholamine specificity in transgenic mice" Proc Natl Acad Sci USA. 89. 1631-1635 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ito,M: "Preservation of an inbred mouse strain by the storage of frozen embryos:An estimate of the time of occurrence of a serum IgG1 deficiency mutation found in MRL-lpr" Lab Anim Sci. 42. 211-213 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sasaoka,T: "Analysis of the human tyrosine hydroxylase promoter-chloramphenicol acetyltransterase chimeric gene expression in transgenic mice" Mol Brain Res. 16. 274-286 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Koike,S: "Poliovirus-sensitive transgenic mice as a new animal model" Dev Biol Stand.

    • Related Report
      1992 Annual Research Report
  • [Publications] Shimano,H: "Plasma lipoprotein metabolism in transgenic mice overexpressing apolipoprotein E:Accelerated clearance of lipoproteins containing apolipoprotein B" J Clin Invest. 90. 2084-2091 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Abeliovich,A: "On somatic recombination in the central nervous system of transgenic mice" Science. 257. 404-408 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takagi,K: "A rapid and efficient protocol of the inverted PCR using two primer pairs" Biotechniqu. 13. 176-178 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Izawa,M: "Inhibition of chemical carcinogenesis in vivo by azatyrosine" Cancer Res. 52. 1628-1630 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kobayashi,K: "Genetic alteration of catecholamine specificity in transgenic mice" Proc Natl Acad Sci USA. 89. 1631-1635 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shimano,H: "Overexpression of apolipoprotein E in transgenic mice:Marked reduction in plasma lipoproteins except higy density lipoprotein and resistance against diet-induced hypercholesterolemia" Proc Natl Acad Sci USA. 89. 1750-1754 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ando,K: "Chemically induced forestomach papillomas in transgenic mice carry mutant human c-Ha-ras transgenes" Cancer Res. 52. 978-982 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Saitoh,S: "De novo production of α2-macroglobulin in cultured astroglia from rat brain" Molecular Brain Research. 12. 155-161 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kunieda,T: "Sexing of mouse preimplantation embryos by detection of Y chromosome-specific sequences using polymerase chain reaction" Biol Reprod. 46. 692-697 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Xian,M: "Sex identification and development of single blastomeres from 2-cell mouse embryos" J Rep Dev. 38. 15-21 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nagamine,CM: "The musculus-type chromosome of the laboratory mouse is of Asian origin" Mammalian Genome. 3. 84-91 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Koide,T: "The amplified long genomic sequence(ALGS)located in the centromeric regions of mouse chromosomes" Genomics. 13. 1186-1191 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nonaka,M: "Molecular cloning of mouse β_2-glycoprotein I and mapping of the gene to chromosome 11" Genomics. 13. 1082-1087 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Suzuki,H: "Compensatory changes in silver-stainability of nucleolar organizer regions in mine" Jpn J Genet. 67. 217-1992 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nonaka,M: "Molecular cloning of the B subunit of mouse coagulation factor XIII and assignment of the gene to chromosome 1:Close evolutionary relationship to complement factor H" Genomics.

    • Related Report
      1992 Annual Research Report
  • [Publications] Shiroishi,T: "Hotspots of meiotec recombination in the mouse major histo compatibility complex" Genetica.

    • Related Report
      1992 Annual Research Report
  • [Publications] Suematsu,S: "Generation of plasmacytomas with the chromosomal translocation t(12;15)in interleukin 6 transgenic mice" Proc Natl Acad Sci USA. 89. 232-235 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Akagi,K: "Strain dependency of cell-type specificity and onset of lymphoma development in Eμ-myc transgenic mice" Jpn Cancer Res. 83. 269-273 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takashima,H: "Characterization of T-cell tolerance to hepatitis B virus(HBV)antigen in transgenic mice" Immunology. 75. 398-405 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamamura,K: "Transgenic mouse as a tool for the study of autoimmune disease:insulin-dependent diabetes mellitus" Int J Immunopharmacol. 14. 451-455 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Zhao,X: "Developmental and liver-specific expression directed by the serum amyloid P component promoter in transgenic mice" J Biochem. 111. 736-738 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Murakami,T: "Effect of serum amyloid P component level on transthyretin-derived amyloid deposition in a transgenic mouse model of familial amyloidotic polyneuropathy" Am J Pathol. 141. 451-456 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nagahata,T: "Inhibition of intrahepatic hepatitis B virus replication by antiviral drugs in a novel transgenic mouse model" Antimicrob Agents Chem. 36. 2042-2045 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Miyazaki,T: "Prevention of autoimmune insulitis in nonobese diabetic mice by expression of major histocompatibility complex class II^d molecules" Proc Natl Acad Sci USA. 89. 9519-9523 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Katsuki,M: "Multistage Carcunogenesis" CRC Press, 403 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kimura,M: "Antisense RNA and DNA" Wiley-Liss Inc, 416 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamamura,K: "Molecular approaches to the study and treatment of human diseases" Elsevier Science Publishers B.V, 455 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamamura,K: "Springer seminars in immunopathology" Springer-Verlag, 199 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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