1989 Fiscal Year Annual Research Report

外来遺伝子DNA導入による新しいモデル動物の開発

Research Project

Project/Area Number	01619001
Research Institution	Tokai University
Principal Investigator	勝木元也東海大学, 医学部・DNA生物学教室, 教授 (20051732)
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細胞遺伝, 教授 (90115197) 近藤寿人名古屋大学, 理学部分子生物学, 教授 (70127083) 木村穣東海大学, 医学部DNA生物学教室, 助教授 (10146706) 大久保博晶京都大学, 医学部附属免疫研究施設第二部門, 助教授 (20094089) 岩倉洋一郎東京大学, 医科学研究所ウイルス感染研究部, 助教授 (10089120)
Keywords	トランスジェニックマウス / 生物機能モデル / ヒト疾患モデル / 家族性アミロイドポリニューロパチー / アンチセンス / 遺伝子標的導入法
Research Abstract	1.研究の目的本研究は、バイオサイエンスの基礎研究にとって重要な役割を果す生物機能モデルおよびヒト疾患モデル動物の開発を、発生工学、遺伝子工学等の方法を駆使して開発し、様々な遺伝子機能を個体レベルで解析する実験系を確立することを目的とする。 2.研究実績遺伝子DNAを受精卵に導入し、個体にまで発生させると、個体の全細胞に導入遺伝子をもつトランスジェニック動物を得ることができる。この方法を用いて、今年度は、いくつかの生物機能モデル動物が得られた。(i)トランスサイレチン(TTR)遺伝子は点突然変異を起すと家族性アミロイドポリニューロパチーを発症する。この遺伝子をマウスに導入したところ、特定の組織にアミロイドの沈着が認められた。(ii)アンチセンスRNAを発現する遺伝子を構築し、トランスジェニックマウスを作成したところ、特定遺伝子の発現が抑制され、優性形質の抑制にも遺伝子導入法が有効であることが確認された。(iii)ラットレニンおよびアンジオテンシノーゲン遺伝子をそれぞれ導入したマウスを作成すると、それぞれのマウスでは血圧は正常であった。ところが、これらを交配して得られたレニンとアンジオテシシノーゲンの双方の遺伝子をもつマウスは、高血圧症を呈した。(iv)HIV、HTLVIなどのウイルス遺伝子導入マウスが得られ、病理症状を示した。以上の結果から、遺伝子導入によって外来性の遺伝形質を発現させ個体での生物現象の変化から、導入遺伝子の機能を解析する方法が確立したといえる。今後は、欧米諸国で成功した遺伝子標的導入法を確立し目的の遺伝子を、計画的に変異させることによって、生物機能モデルを作り、解析していきたいと考えている。

Research Products

(40 results)

All Other

All Publications (40 results)

[Publications] Katsuki M.,Kimura M.,et al.: "Lymphocyte infiltration into cerebellum in transgenic mice carrying human ILー2 gene." Int.Immunol.1. 214-218 (1989)
[Publications] Bonneville M.,Katsuki M.,et al.: "Blockage of αβ Tーcell development by TCR γδ transgenes." Nature. 342. 931-934 (1989)
[Publications] Fukamizu A.,Katsuki M.,et al.: "Tissueーspecific expression of the human renin gene in transgenic mice." Biochem.Biophys.Res.Commun.165. 826-832 (1989)
[Publications] Katsuki M.,Kimura M.,et al.: "Embryonal tumors from transgenic mouse zygotes carring human activated cーHaーras genes." Mol.Biol.Med.6. (1989)
[Publications] Bonneville M.,Katsuki M.,et al.: "Transgnic mice demonstrate that epothlial homing of γδ T cells is determined by cell lineages independent of T cell receptor specificity." Cold Spring Harbor Symposia on Quantitative Biology. 54. (1989)
[Publications] Miyashita S.,Ikeda J.,et al.: "Linear plasmid DNAs of the plant pathogenic fungus Rhizoctonia solani with unique terminal structures." Mol.Gen.Genet.220. 165-171 (1990)
[Publications] Kondo I.,Ikeda J.,et al.: "Exclusion mapping of the hereditary dentatorubrollidolusian atrophy gene from Huntington's disease locus." J.Med.Genet.2. (1990)
[Publications] Iwakura Y.: "Mechanism of blastocyst formation of the mouse embryo." Dev.Growth Differ.31. 523-529 (1990)
[Publications] Asano M.,Iwakura Y.,et al.: "Induction of interferonーα by interferonーβ,but not of interferonーβ by interferonーα,in the mouse." Virology. 175. (1990)
[Publications] Maekawa K.,Ohkubo H.,et al.: "Cloning and sequence analysis of cDNA encoding a precursor for porcine brain natriuretic peptide." Biochem.Biophys.Res.Commun.157. 410-416 (1989)
[Publications] Murai T.,Ohkubo H.,et al.: "Molecular cloning and sequence analysis of human qenomic DNA encoding a novel membrane protein which exhibits a slowly activating potassium channel activity." Biochem.Biophys.Res.Commun.161. 176-181 (1989)
[Publications] Yokota Y.,Ohkubo H.,et al.: "Molecular characterization of a functional cDNA for rat substance P receptor." J.Biol.Chem.264. 17649-17652 (1989)
[Publications] Kimura M.,Katsuki,M.,et al.: "Restoration of myelin formation by a single type of myelin basic protein in transgenic shiverer mice" Proc.Natl.Acad.Sci.USA. 86. 5661-5665 (1989)
[Publications] Koji T.,Kimura M.,et al.: "In situ localization of cーMYC mRNA in HLー60 cells using nonーradioactive synthetic oligodeoxynucleotide probes." Acta Histochem.Cytochem.22. 295-307 (1989)
[Publications] Inoue K.,Kondoh H.,et al.: "Stageーdependent expression of the chicken δーcystallin gene in transgenic fish embryos." Cell Differ.Develop.27. 57-68 (1989)
[Publications] Kato K.,Kondoh H.,et al.: "Rapid and transient decrease of Nーmyc expression in retinoic acidーinduced differentiation of OTF9 teratocarcinoma stem cells." Mol.Cell.Biol.10. (1990)
[Publications] Goto K.,Kondoh H.,et al.: "Functional cooperation of lensーspecific and nonspecific elements in the 1ーcrystallin enhancer." Mol.Cell.Biol.10. (1990)
[Publications] Sawai S.,Kondoh H.,et al.: "Oraganization and expression of the chickin Nーmyc gene." Mol.Cell Biol.10. (1990)
[Publications] Wakamatsu Y.,Kondoh H.: "Conditions for detection of embryonic Nーmyc expression by in situ hybridization." Acta Histochem.Cytochem.(1990)
[Publications] Kondoh H.: "The mechanism of δ1ーcrystallin gene regulation:cooperation of lensーspecific and nonーspecific elements." Dev.Growth Differ.32. (1990)
[Publications] Nikaido T.,Nishida Y.,et al.: "Loss in transformed cells of cell cycle regulation of expression of a nuclear protein recognized by SLE patient antisera." Exp.Cell Res.182. 284-289 (1989)
[Publications] Nikaido T.,Nishida Y.,: "Cloning and nucleotide sequence of cDNA for Ki ant gen,a hithly conserved nuclear protein detected with sera from patients with systemic lupus erythematosus." Clin.Exp.Immunol.(1990)
[Publications] Yamaguchi M.,Nishida Y.,et al.: "Drosophila preoliferating cell nuclear antigen(cyclin)gene:structure,expression during development,and specific binding of homeodomain proteins to its 5'ーflanking region" Mol.Cell Biol.(1990)
[Publications] Hashimoto N.,et al.: "Germ cell deficiency cause testis cord differertiation in reconstituted mouse fetal ovaries." J.Exp.Zool. 253. 61-70 (1990)
[Publications] Momoi MY.,Hanaoka K.,et al.: "The expression of cellular retinoic acid binding protein(CRABP)in the neural tube and notochord of mouse embryo." Proc.Japan Acid.65. 9-12 (1989)
[Publications] Obaru K.,Maeda S.,et al.: "A cーDNA clone inducible in human tonsillar lymphocyte by a tumor promoter codes for a novel protein of theーthromboglobulin superfamily" Mol.Immunol.26. 423-426 (1989)
[Publications] Ueyama H.,Maeda S.,et al.: "Antithrombin III kumamoto:Identification of a point mutation and genotype analysis of the family." Thromb Haemostas. (1990)
[Publications] Uehira M.,Yamamura K.,et al.: "Development of autoimmune insulitis is prevented in E d but not in A k NOD transgenic mice." Int.Immunol.1. 209-213 (1989)
[Publications] Shimada K.,Maeda.,et al.: "Transgenic mouse model of famillial amyloidotic polyneruopathy." Mol.Biol.Med. 6. 333-343 (1989)
[Publications] Miyazaki J.,Yamamura K.,et al.: "Expression vector system based on the chickenーactin promotor directs efficient production of interleukinー5." Gene. 79. 269-277 (1989)
[Publications] Iwanaga T.,Maeda S.,Yamamura K.,et al.: "Liverーspecific and highーlevel expression of human serum amyloid P component gene in transgenic mice." Dev.Genet.10. 365-371 (1989)
[Publications] Murakami T.,Yamamura K.,et al.: "Tissueーand developmental stageーspecific expression of the rat ornithine carbomoyltransferase gene in transgenic mice." Dev.Genet. 10. 393-401 (1989)
[Publications] Iwakura Y.,et al.: "The Biology of Interferon System 1988" Kodansha Scientific Ltd., pp335-340 (1988)
[Publications] Iwakura Y.,et al.: "Development of Preimplantation Embryos and Their Environment" Alan R.Liss,Inc., pp199-210 (1989)
[Publications] Nakanishi S.,Ohkubo H.,et al.: "Kinins V,Part A" Plenum Publishing Co., pp7-18 (1989)
[Publications] Nakanishi S.,Ohkubo h.,et al.: "NATO ASI Series Vol H32,Molecular Biology of Neuroreceptors and lon Channels" SpringerーVerlag, pp269-277 (1989)
[Publications] Ohnishi S.,Maeda S.,et al.: "Amyloid and Amiloidosis" Plenum Publishing Co., pp35-40 (1989)
[Publications] Mita S.,Maeda S.,et al.: "Amyloid and Amilidosis" Plenum Publishing Co., pp361-364 (1988)
[Publications] Wakasugi S.,Maeda S.,et al.: "Amyloid and Amiloidosis" Plenum Publishing Co., pp393-398 (1988)
[Publications] Murakami T.,Maeda S.,et al.: "Amyloid and Amiloidosis" Pleunum Publishing Co., pp405-409 (1988)

1989 Fiscal Year Annual Research Report

外来遺伝子DNA導入による新しいモデル動物の開発

Principal Investigator

勝木 元也 東海大学, 医学部・DNA生物学教室, 教授 (20051732)

Research Products

[Publications] Katsuki M.,Kimura M.,et al.: "Lymphocyte infiltration into cerebellum in transgenic mice carrying human ILー2 gene." Int.Immunol.1. 214-218 (1989)

[Publications] Bonneville M.,Katsuki M.,et al.: "Blockage of αβ Tーcell development by TCR γδ transgenes." Nature. 342. 931-934 (1989)

[Publications] Fukamizu A.,Katsuki M.,et al.: "Tissueーspecific expression of the human renin gene in transgenic mice." Biochem.Biophys.Res.Commun.165. 826-832 (1989)

[Publications] Katsuki M.,Kimura M.,et al.: "Embryonal tumors from transgenic mouse zygotes carring human activated cーHaーras genes." Mol.Biol.Med.6. (1989)

[Publications] Bonneville M.,Katsuki M.,et al.: "Transgnic mice demonstrate that epothlial homing of γδ T cells is determined by cell lineages independent of T cell receptor specificity." Cold Spring Harbor Symposia on Quantitative Biology. 54. (1989)

[Publications] Miyashita S.,Ikeda J.,et al.: "Linear plasmid DNAs of the plant pathogenic fungus Rhizoctonia solani with unique terminal structures." Mol.Gen.Genet.220. 165-171 (1990)

[Publications] Kondo I.,Ikeda J.,et al.: "Exclusion mapping of the hereditary dentatorubrollidolusian atrophy gene from Huntington's disease locus." J.Med.Genet.2. (1990)

[Publications] Iwakura Y.: "Mechanism of blastocyst formation of the mouse embryo." Dev.Growth Differ.31. 523-529 (1990)

[Publications] Asano M.,Iwakura Y.,et al.: "Induction of interferonーα by interferonーβ,but not of interferonーβ by interferonーα,in the mouse." Virology. 175. (1990)

[Publications] Maekawa K.,Ohkubo H.,et al.: "Cloning and sequence analysis of cDNA encoding a precursor for porcine brain natriuretic peptide." Biochem.Biophys.Res.Commun.157. 410-416 (1989)

[Publications] Murai T.,Ohkubo H.,et al.: "Molecular cloning and sequence analysis of human qenomic DNA encoding a novel membrane protein which exhibits a slowly activating potassium channel activity." Biochem.Biophys.Res.Commun.161. 176-181 (1989)

[Publications] Yokota Y.,Ohkubo H.,et al.: "Molecular characterization of a functional cDNA for rat substance P receptor." J.Biol.Chem.264. 17649-17652 (1989)

[Publications] Kimura M.,Katsuki,M.,et al.: "Restoration of myelin formation by a single type of myelin basic protein in transgenic shiverer mice" Proc.Natl.Acad.Sci.USA. 86. 5661-5665 (1989)

[Publications] Koji T.,Kimura M.,et al.: "In situ localization of cーMYC mRNA in HLー60 cells using nonーradioactive synthetic oligodeoxynucleotide probes." Acta Histochem.Cytochem.22. 295-307 (1989)

[Publications] Inoue K.,Kondoh H.,et al.: "Stageーdependent expression of the chicken δーcystallin gene in transgenic fish embryos." Cell Differ.Develop.27. 57-68 (1989)

[Publications] Kato K.,Kondoh H.,et al.: "Rapid and transient decrease of Nーmyc expression in retinoic acidーinduced differentiation of OTF9 teratocarcinoma stem cells." Mol.Cell.Biol.10. (1990)

[Publications] Goto K.,Kondoh H.,et al.: "Functional cooperation of lensーspecific and nonspecific elements in the 1ーcrystallin enhancer." Mol.Cell.Biol.10. (1990)

[Publications] Sawai S.,Kondoh H.,et al.: "Oraganization and expression of the chickin Nーmyc gene." Mol.Cell Biol.10. (1990)

[Publications] Wakamatsu Y.,Kondoh H.: "Conditions for detection of embryonic Nーmyc expression by in situ hybridization." Acta Histochem.Cytochem.(1990)

[Publications] Kondoh H.: "The mechanism of δ1ーcrystallin gene regulation:cooperation of lensーspecific and nonーspecific elements." Dev.Growth Differ.32. (1990)

[Publications] Nikaido T.,Nishida Y.,et al.: "Loss in transformed cells of cell cycle regulation of expression of a nuclear protein recognized by SLE patient antisera." Exp.Cell Res.182. 284-289 (1989)

[Publications] Nikaido T.,Nishida Y.,: "Cloning and nucleotide sequence of cDNA for Ki ant gen,a hithly conserved nuclear protein detected with sera from patients with systemic lupus erythematosus." Clin.Exp.Immunol.(1990)

[Publications] Yamaguchi M.,Nishida Y.,et al.: "Drosophila preoliferating cell nuclear antigen(cyclin)gene:structure,expression during development,and specific binding of homeodomain proteins to its 5'ーflanking region" Mol.Cell Biol.(1990)

[Publications] Hashimoto N.,et al.: "Germ cell deficiency cause testis cord differertiation in reconstituted mouse fetal ovaries." J.Exp.Zool. 253. 61-70 (1990)

[Publications] Momoi MY.,Hanaoka K.,et al.: "The expression of cellular retinoic acid binding protein(CRABP)in the neural tube and notochord of mouse embryo." Proc.Japan Acid.65. 9-12 (1989)

[Publications] Obaru K.,Maeda S.,et al.: "A cーDNA clone inducible in human tonsillar lymphocyte by a tumor promoter codes for a novel protein of theーthromboglobulin superfamily" Mol.Immunol.26. 423-426 (1989)

[Publications] Ueyama H.,Maeda S.,et al.: "Antithrombin III kumamoto:Identification of a point mutation and genotype analysis of the family." Thromb Haemostas. (1990)

[Publications] Uehira M.,Yamamura K.,et al.: "Development of autoimmune insulitis is prevented in E d but not in A k NOD transgenic mice." Int.Immunol.1. 209-213 (1989)

[Publications] Shimada K.,Maeda.,et al.: "Transgenic mouse model of famillial amyloidotic polyneruopathy." Mol.Biol.Med. 6. 333-343 (1989)

[Publications] Miyazaki J.,Yamamura K.,et al.: "Expression vector system based on the chickenーactin promotor directs efficient production of interleukinー5." Gene. 79. 269-277 (1989)

[Publications] Iwanaga T.,Maeda S.,Yamamura K.,et al.: "Liverーspecific and highーlevel expression of human serum amyloid P component gene in transgenic mice." Dev.Genet.10. 365-371 (1989)

[Publications] Murakami T.,Yamamura K.,et al.: "Tissueーand developmental stageーspecific expression of the rat ornithine carbomoyltransferase gene in transgenic mice." Dev.Genet. 10. 393-401 (1989)

[Publications] Iwakura Y.,et al.: "The Biology of Interferon System 1988" Kodansha Scientific Ltd., pp335-340 (1988)

[Publications] Iwakura Y.,et al.: "Development of Preimplantation Embryos and Their Environment" Alan R.Liss,Inc., pp199-210 (1989)

[Publications] Nakanishi S.,Ohkubo H.,et al.: "Kinins V,Part A" Plenum Publishing Co., pp7-18 (1989)

[Publications] Nakanishi S.,Ohkubo h.,et al.: "NATO ASI Series Vol H32,Molecular Biology of Neuroreceptors and lon Channels" SpringerーVerlag, pp269-277 (1989)

[Publications] Ohnishi S.,Maeda S.,et al.: "Amyloid and Amiloidosis" Plenum Publishing Co., pp35-40 (1989)

[Publications] Mita S.,Maeda S.,et al.: "Amyloid and Amilidosis" Plenum Publishing Co., pp361-364 (1988)

[Publications] Wakasugi S.,Maeda S.,et al.: "Amyloid and Amiloidosis" Plenum Publishing Co., pp393-398 (1988)

[Publications] Murakami T.,Maeda S.,et al.: "Amyloid and Amiloidosis" Pleunum Publishing Co., pp405-409 (1988)

勝木元也東海大学, 医学部・DNA生物学教室, 教授 (20051732)