• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

単一遺伝子病の分子・細胞生物学的研究

Research Project

Project/Area Number 04206101
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionTohoku University (1993-1994)
Kyushu University (1992)

Principal Investigator

多田 啓也 (1993-1994)  東北大学, 医学部, 名誉教授 (20046907)

勝木 元也 (1992)  九州大学, 生体防御医学研究所, 教授 (20051732)

Co-Investigator(Kenkyū-buntansha) 成澤 邦明  東北大学, 医学部, 教授 (90004647)
勝沼 信彦  徳島文理大学, 健康科学研究所, 教授 (50035375)
森 正敬  熊本大学, 医学部, 教授 (40009650)
松田 一郎  熊本大学, 医学部, 教授 (10000986)
香川 靖雄  自治医科大学, 教授 (30048962)
権藤 洋一  東海大学, 医学部, 助手 (40225678)
岩倉 洋一郎  東京大学, 医科学研究所, 助教授 (10089120)
近藤 寿人  名古屋大学, 理学部, 教授 (70127083)
山村 研一  熊本大学, 医学部, 教授 (90115197)
Project Period (FY) 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥78,000,000 (Direct Cost: ¥78,000,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥20,000,000 (Direct Cost: ¥20,000,000)
Fiscal Year 1992: ¥55,000,000 (Direct Cost: ¥55,000,000)
Keywords単一遺伝子病 / 分子生物学 / 遺伝子単離 / 病因変異 / 遺伝子解析 / 遺伝子診断 / 遺伝子治療 / トランスジェニックマウス / ジーンターゲッティング / ヒト疾患モデル / 生物機能モデル / 胚幹細胞 / 遺伝子欠損モデル / トランスサイレチン / HTLVI
Research Abstract

本研究班は遺伝病の予防・治療法の開発を目指すとともに、これらの疾患の分子レベルの究明を通じてヒトにおける遺伝子発現や調節機構の未知の部分を解明することを目的として3年間にわたって研究を進め、その研究成果は国際的にも高く評価されている。本研究班で世界に先駆けて単離された遺伝子は実に30個の多きを数えた。一方では、より多くの未知の病因遺伝子をより簡単に単離するための研究が進められ、病因遺伝子の探索-特にポジシナルクローニングに必要なRFLPマカ-を570個同定し、又、染色体バンドレベルにマップ出来たコスミッドクローンは約3000個である。発症の分子機構を明らかにした疾患は先天性酵素異常症、レセプター・転送系蛋白質・血清蛋白質異常症、細胞小器官異常症など多岐にわたり、総計42疾患に及ぶ。これらの成果は遺伝子診断に利用され、保因者診断や出生前診断、発症前診断がなされている。多くのミトコンドリアの機能が核遺伝子によって支配され、ミトコンドリア遺伝子の異常を基礎として老化とともに発症してくる糖尿病や心疾患、神経疾患の解決にはミトコンドリアを支配している核遺伝子の解明が不可欠であることを明らかにした。トランスジェニックマウスやジーンターゲッティングで作成したモデル動物で遺伝病の発症過程の解析がなされ、また遺伝子治療に向けての新しい遺伝子導入法の検討がなされた。遺伝子治療へ向けてのベクターの作製では短期間に高い力価をもつレトロウイルスベクターの作製、HVJ-リポゾームの開発がなされた。これらの成果をA4版、300頁の報告書にまとめ公表した。これを基盤として遺伝子の研究が更に大きく発展し、医療・医学の進歩に貢献し続けることを念ずる。

Report

(2 results)
  • 1994 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Yao,Y.et al.: "Rapid detection of phenylketonuria mutations by non-radioactive single-strand conformation polymorphism." Acta Paediatrica Japonica. 36. 231-235 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Suzuki,Y.et al.: "Isolation and characterization of mutations human holocarboxylase synthetase cDNA." Nature Genetics. 8. 122-128 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ogasawara,M.et al: "Identification of two novel mutations in the methlmalonyl-CoA mutase gene with decreased levels of mRNA in methylmalonic acidemia." Human Molecular Genetics. 3. 867-872 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Chiba,Y.et al.: "Purification and properties of bovine liver holocarboxylase synthetase" Archives of Biochemistry and Biophysics. 313. 8-14 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Aoki,M.et al.: "Familial amyotrophic lateral sclerosis(ALS)in Japan assosiated with H46R mutation in Cu/Zn superoxide dismutase gene." Journal of Neurological Sciences. 126. 77-83 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sugiyama,N.et al.: "Urinary propionylcarnitine analysis for monitorning carnitine supplementation in inherited disorders of propionate metabolism." Journal of Inherited Metabolic Disease. 17. 611-615 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sasaoka,T.: "Analysis of the human tyrosine hydroxylase promoter-chloram-phenicol acetyltransferase chimeric gene expression in transgenic mice." Mol.Brain Res.16. 274-286 (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." Biotechniques. 13. 176-178 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hayashi,T.: "RNA packing signal of human immunodeficiency virus type 1." Virology. 188. 590-599 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Iwakura,Y.: "The induction of cataracts by HIV-I in transgenic mice." AIDS. 6. 1069-1075 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kawahara,T.: "Ribozymes for specific inhibition of mRNA function in the nematode Caenorhabditis elegans.1" Nucleic Acids Symp Ser.27. 45-46 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Aroian,RV.: "Splicing in Caenorhabditis elegans does not require an AG at the 3' splice acceptor site." Mol.Cell Biol.13. 626-702 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sasai,Y.: "Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of Split." Genes Dev.6. 2620-2634 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Akazawa,C.: "Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system." J.Biol.Chem.267. 21879-21885 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sawada,M.: "Stable expression of monkey cytochrome p-450IAL cDNA in Chinese hamster CHL cells and its application for detection of mutagenicity of aflatoxin B_1." Mutation Res.265. 23-29 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Fukuta,H.: "Toxicological significance of dog liver cytochrome p-450:Examination with the enzyme expressed in Saccharomyces cerevisiae using recombinant expression plasmid." Mutation Res.269. 97-105 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sawai,S.: "Defects of embryonic organogenesis resulting from targeted disruption of the N-myc gene of the mouse." Development. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Wakamatsu,Y.: "Transition of localization of the N-myc protein from nucleus to cytoplasm in differentiating neurons." Neuron. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Gondo,Y.: "High-frequency genetic reversion mediated by a DNA duplication:The mouse pink-eyed unstable mutation." Proc.Natl.Acad.Sci.USA. 90. 297-301 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Gardner,JM.: "The mouse pink-eyed dilution gene.Association with human Prader-Willi and Angelman Syndromes." Science. 257. 1121-1124 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yoshioka,K.: "Production of a unique multi-lamella structure in the nuclei of yeast expression Drosophila copia gag precursor." FEBS. 302. 5-7 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yoshioka,K.: "Efficient amplification of Drosophila simulans copia directed by high-level reverse transcriptase activity associated with copia virus-like particles." Gene. 120. 191-196 (1992)

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

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

    • Related Report
      1992 Annual Research Report
  • [Publications] Katsuki,M.: "Chemically induced tumors in transgenic mice carrying prototype human c-Ha-ras genes.Multistage Carcinogenesis." CRC Press,Tpkyo, 249-257 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kimura,M.: "Manipulation of myelin formation in transgenic mice.Antisense RNA and DNA." Wiley-Liss,Inc., 109-120 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takiguchi,M.: "Structureand ewpression of the urea cycle enzyme genes.Frontiers and new horizons in amino acid research." Elsevier Science Publishers, 145-150 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takiguchi,M.: "Structure and expression of liver-type arginase gene.Guanidino compounds in biology and medicine." John Libbey&Company, 349-353 (1992)

    • Related Report
      1992 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi