1992 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	04206103
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・附属遺伝発生医学研究施設, 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・免疫研究施設第二, 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	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	本研究は現代のバイオサイエンスの基礎である遺伝子工学と発生工学とを駆使し、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。この目的の遂行のために、計画班として「野生遺伝子導入動物」班、「DNA導入動物」班および「系統化」班を設定し、これらの班および公募班員の評価、研究計画の立案、公開シンポジウム等を行うために総括班を設けた。各研究班員の研究成果報告のとりまとめを行ない、「野生遺伝子導入動物」班、「DNA導入動物」班、「系統化」班からそれぞれ2名を選抜し、合同シンポジウムを行った。その結果、本研究班の評価として、ヒト疾患モデルや生物機能モデル動物の開発と確立に、野生遺伝子導入法やDNA導入法が不可欠の方法になったことが確認された。具体的には、ポリオウイルス受容体遺伝子導入マウスや色素性乾皮症遺伝子欠損マウスが開発され、それぞれの遺伝子の特徴や疾患の発症を大動物や稀少動物を用いずにマウスによって研究できることが確認された。また発生工学技術の応用として、体外受精、凍結保存、卵巣移植等を組み合わせれば、大量の同一遺伝子をもつマウスを計画的に生産し、実験に用いることができることが再度、がん発症マウスを用いて確認された。これまでは、個体で系統を維持生産しながら実験を続けるため、労力や経費やスペースを必要とした。しかし、新しい技術を組合わせて用いれば、マウス個体を飼育する必要はなく、必要に応じて凍結をもどせばよいので、これまでの負担を大きく軽減するものであるといえる。本年度は本研究の最終年度にあたるため、計画研究班員はもちろん公募班員についても6年間の成果をまとめ、来年度発表できるよう報告の準備を行った。研究成果報告書は総括班が各班員の今年度の論文をまとめ別に冊子として作製した。

Research Products

(32 results)

All Other

All Publications (32 results)

[Publications] Kobayashi,K: "Gemetic alteration of catecholamine specificity in transgenic mice" Proc Natl Acad Sci USA. 89. 1631-1635 (1992)
[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)
[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)
[Publications] Koike,S: "Poliovirus-sensitive transgenic mice as a new animal model" Dev Biol Stand.
[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)
[Publications] Abeliovich,A: "On somatic recombination in the central nervous system of transgenic mice" Science. 257. 404-408 (1992)
[Publications] Takagi,K: "A rapid and efficient protocol of the inverted PCR using two primer pairs" Biotechniqu. 13. 176-178 (1992)
[Publications] Izawa,M: "Inhibition of chemical carcinogenesis in vivo by azatyrosine" Cancer Res. 52. 1628-1630 (1992)
[Publications] Kobayashi,K: "Genetic alteration of catecholamine specificity in transgenic mice" Proc Natl Acad Sci USA. 89. 1631-1635 (1992)
[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)
[Publications] Ando,K: "Chemically induced forestomach papillomas in transgenic mice carry mutant human c-Ha-ras transgenes" Cancer Res. 52. 978-982 (1992)
[Publications] Saitoh,S: "De novo production of α2-macroglobulin in cultured astroglia from rat brain" Molecular Brain Research. 12. 155-161 (1992)
[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)
[Publications] Xian,M: "Sex identification and development of single blastomeres from 2-cell mouse embryos" J Rep Dev. 38. 15-21 (1992)
[Publications] Nagamine,CM: "The musculus-type chromosome of the laboratory mouse is of Asian origin" Mammalian Genome. 3. 84-91 (1992)
[Publications] Koide,T: "The amplified long genomic sequence(ALGS)located in the centromeric regions of mouse chromosomes" Genomics. 13. 1186-1191 (1992)
[Publications] Nonaka,M: "Molecular cloning of mouse β_2-glycoprotein I and mapping of the gene to chromosome 11" Genomics. 13. 1082-1087 (1992)
[Publications] Suzuki,H: "Compensatory changes in silver-stainability of nucleolar organizer regions in mine" Jpn J Genet. 67. 217-1992 (1992)
[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.
[Publications] Shiroishi,T: "Hotspots of meiotec recombination in the mouse major histo compatibility complex" Genetica.
[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)
[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)
[Publications] Takashima,H: "Characterization of T-cell tolerance to hepatitis B virus(HBV)antigen in transgenic mice" Immunology. 75. 398-405 (1992)
[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)
[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)
[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)
[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)
[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)
[Publications] Katsuki,M: "Multistage Carcunogenesis" CRC Press, 403 (1992)
[Publications] Kimura,M: "Antisense RNA and DNA" Wiley-Liss Inc, 416 (1992)
[Publications] Yamamura,K: "Molecular approaches to the study and treatment of human diseases" Elsevier Science Publishers B.V, 455 (1992)
[Publications] Yamamura,K: "Springer seminars in immunopathology" Springer-Verlag, 199 (1992)

1992 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] Kobayashi,K: "Gemetic alteration of catecholamine specificity in transgenic mice" Proc Natl Acad Sci USA. 89. 1631-1635 (1992)

[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)

[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)

[Publications] Koike,S: "Poliovirus-sensitive transgenic mice as a new animal model" Dev Biol Stand.

[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)

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

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

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

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

[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)

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

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

[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)

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

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

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

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

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

[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.

[Publications] Shiroishi,T: "Hotspots of meiotec recombination in the mouse major histo compatibility complex" Genetica.

[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)

[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)

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

[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)

[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)

[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)

[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)

[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)

[Publications] Katsuki,M: "Multistage Carcunogenesis" CRC Press, 403 (1992)

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

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

[Publications] Yamamura,K: "Springer seminars in immunopathology" Springer-Verlag, 199 (1992)

野村達次 (財)実験動物中央研究所, 所長 (10072399)