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標的遺伝子組換えによる突然変異体の作成とその生体機能の研究

Research Project

Project/Area Number 05275102
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionThe University of Tokyo (1995-1996)
Kyushu University (1993-1994)

Principal Investigator

勝木 元也  東京大学, 医学研究所, 教授 (20051732)

Co-Investigator(Kenkyū-buntansha) 前田 秀一郎  山梨医学大学, 生化学第一, 教授 (10117244)
林崎 良英  理化研, ライフ・筑波研究センター, 主任研究員 (70192705)
金田 安史  大阪大学, 細胞生体工学センター, 助教授 (10177537)
糸原 重美  京都大学, ウイルス研究所, 助教授 (60252524)
村松 喬  名古屋大学, 医学部, 教授 (00030891)
相沢 慎一  熊本大学, 医学部, 教授 (60073011)
木村 穣  東海大学, 医学部, 助教授 (10146706)
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥359,000,000 (Direct Cost: ¥359,000,000)
Fiscal Year 1996: ¥105,000,000 (Direct Cost: ¥105,000,000)
Fiscal Year 1995: ¥90,000,000 (Direct Cost: ¥90,000,000)
Fiscal Year 1994: ¥84,000,000 (Direct Cost: ¥84,000,000)
Fiscal Year 1993: ¥80,000,000 (Direct Cost: ¥80,000,000)
Keywords標的遺伝子組換え / ジーンターゲッティング / 中枢神経系 / 免疫系 / 形態形成 / ras / ドーパミン受容体 / 突然変異 / グルタミン酸受容体 / H-ras / セロトニン受容体 / p53
Research Abstract

本研究は標的遺伝子組換え(ジーンターゲッティング)を用いて、中枢神経系、免疫系、形態形成等に関与する遺伝子を計画的に破壊し、それぞれの遺伝子の生体での機能を解析することを目的としている。計画班員は、きわめて緊密に連携し、独立を保ちながら、多種の遺伝子の突然変異体の作成に成功した。
本年度までに本研究班によって作成された突然変異マウスを列挙すれば120種を越えるに至った。グルタミン酸受容体、ドーパミン受容体、セロトニン受容体、リアノジン受容体、IP3受容体、H-ras、N-ras、K-ras、rac1、rac2、basigin、prion、SAPなどである。それぞれの遺伝子破壊によって認められる生体の特徴は、細胞レベルや分子レベルの成果から容易に予測されものは少なく、それぞれの遺伝子産物が多彩な生体機能に関わっていることが示された。行動異常や記憶・学習の実験により高次機能の解析を行った。その結果、ras群遺伝子産物は細胞の増殖と分化だけでなく、脳の高次機能にも関与していることが明らかとなった。
ジーンターゲッティングマウスが次々に作成され、その解析の結果が今後報告される。

Report

(4 results)
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (193 results)

All Other

All Publications (193 results)

  • [Publications] Kadotani,H.,et al: "Motor discoordination results from combined gene disruption of the NMDA receptor NR2A and NR2C subunits,but not from single disruption of the NR2A or NR2C subunits." J Neurosci. 16. 7859-7867 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokoi,M.,et al: "Impariment of hippocampal mossy fiber LTD in mice lacking mGluR2." Science. 273. 645-647 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kato,T.,et al: "Inactivation of hepatitis C virus cDNA transgene by hypermethylation intrangensic mice." Arch Virol. 141. 951-958 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Inoue,R.,et al: "Rare activation of the human c-Ha-ras transgene of mice in hemangioendothelial sarcomas and liver tumors induced by Glu-P-1." Jpn J Cancer Res. 87. 583-588 (1996)

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      1996 Annual Research Report
  • [Publications] Ohbo,K.,et al: "Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor gamma chain." Blood. 87. 956-967 (1996)

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      1996 Annual Research Report
  • [Publications] Li,Y.,et al: "Establishiment of transgenic mice carrying human fetus-specific CYP3A7." Arch Biochem Biophys. 329. 235-240 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Gondo,Y.,et al: "A novel positive detection system of in vivo mutations in rpsL(strA)transgenic mice." Mutation Res. 360. 1-14 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Norimura,T.,et al: "p53-dependent apoptosis suppresses radeation-induced teratogenesis." Nature Medicine. 2. 577-580 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamaguchi,H.,et al: "Dopamine D2 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituitary." Genes to Cells. 1. 253-268 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tokita,Y.,et al: "Characterization of excitatory amino acid neurotoxicity in N-methy1-D-aspartate receptor-deficient mouse cortical neuronal cells." Eur J Neurosci. 8. 69-78 (1996)

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      1996 Annual Research Report
  • [Publications] Shinohara,T.,et al: "Resistance to cutaneous graft-vs.-host disease is not induced in TCRδ gene mutant mice." J Exp Med. 183. 1483-1489 (1996)

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      1996 Annual Research Report
  • [Publications] Shibuki,K.,et al: "Deficient cerebellar long-term depression,impaired eyeblink conditioning,and normal motor coordination in GFAP mutant mice." Neuron. 16. 587-599 (1996)

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      1996 Annual Research Report
  • [Publications] Yokoyama,T.,et al: "Detection of species specific epitopes of mouse and hamster prion protein(PrPs)by anti-peptide antibodies." Arch Virol. 141. 763-769 (1996)

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      1996 Annual Research Report
  • [Publications] Kawaguchi,H.,et al: "In vivo gene transfection of human ecNOS in cardiomyocytes causes apoptosis-like cell death." Circulation. (in press).

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      1996 Annual Research Report
  • [Publications] Sato,M.,et al: "Analysis of nuclear localization of laminin binding protein precursor p40(LBP/p40)." Biochem Biophys Res Comm. (in press)

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      1996 Annual Research Report
  • [Publications] Kaneda,Y.,et al: "Prevention of restenosis by gene therapy." Ann NY Acad Sci. (in press)

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      1996 Annual Research Report
  • [Publications] Tomita,N.,et al: "In vivo gene transfer of insulin gene into neonatal rats by HVJ-liposome method resulted in sustained transgene expression." Gene Therapy. 3. 477-482 (1996)

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      1996 Annual Research Report
  • [Publications] Akagi,S.,et al: "In vivo transfection of antisense oligodeoxynucleotides for transforming growth factor-beta 1 into the kidney suppressed glomerulosclerosis and induction of alpha-smooth muscle actin in experimental glomerulonephritis." Kidney Inter. 50. 148-155 (1996)

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      1996 Annual Research Report
  • [Publications] Isaka,Y.,et al: "Gene therapy by skeletal muscle expression of decorin prevents fibrotic disease in rat kidney." Natute Medicine. 2. 418-423 (1996)

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      1996 Annual Research Report
  • [Publications] Yanagihara,I.,et al: "Expression of full-length human dystrophin cDNA in mdx mouse muscle by HVJ-liposome." Gene Therapy. 3. 549-553 (1996)

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      1996 Annual Research Report
  • [Publications] Nakamura,N.,et al: "Transient introduction of a foreign gene into healing rat patellar ligament." J Clin Invest. 97. 226-231 (1996)

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      1996 Annual Research Report
  • [Publications] Hayashi,S-I.,et al: "In vivo transfer of gene and oligodeoxynucleotides into skin of fetal rats by incubation in amniotic fluid." Gene Therapy. 3. 878-885 (1996)

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      1996 Annual Research Report
  • [Publications] Yonemitsu,Y.,et al: "Characterization of in vivo gene tranfer into the arterial wall mediated by the Sendai Virus(Hemaggulutinating Virus of Japan)liposomes:An effective tool for the in vivo study of arterial diseases." Leboratory Investigation. 75. 313-323 (1996)

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      1996 Annual Research Report
  • [Publications] Ellison,K-E.,et al: "Fusigenic liposome mediated DNA transfer into cardiac myocytes." J Mol Cell Cardiology. 28. 1385-1399 (1996)

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      1996 Annual Research Report
  • [Publications] Dzau,V.J.,et al: "Fusigenic viral liposome for gene therapy in cardiovascular diseases." Proc Natl Acad Sci USA. 93. 11421-11425 (1996)

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      1996 Annual Research Report
  • [Publications] Morishita,R.,et al: "Role of transcriptional cis-elements,angiotensinogen gene-activating elements,of angiotensinogen gene in blood pressure regulation." Hypertension. 27. 502-507 (1996)

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      1996 Annual Research Report
  • [Publications] Yamada,K.,et al: "Efficient oligonucleotides delivery using the HVJ-liposome method in the central nervous system." Am J Physiol. 271. R1212-R1220 (1996)

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      1996 Annual Research Report
  • [Publications] Kitamoto,T.,et al: "Humanized prion protein knock-in by Cre-induced site-specific recombination in the mouse." Biochem Biophys Res Commun. 222. 742-747 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hoque,MZ.,et al: "Mutation in the prion protein gene at codon 232 in Japanese patients with Creutzfeldt Jakob disease;a clinicopathological,immunohistochemical and transmission study." Acta Neuropathol. 92. 441-446 (1996)

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      1996 Annual Research Report
  • [Publications] Ghetti,B.,et al: "Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles:The phenotype of the stop codon 145 mutation in PRNP." Proc Natl Acad Sci USA. 93. 744-748 (1996)

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      1996 Annual Research Report
  • [Publications] Tateishi,J.,et al: "Experimental transmisson of Creutzfeldt-Jakob disease and related diseases to rodents." Neurology. 46. 532-537 (1996)

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      1996 Annual Research Report
  • [Publications] Kitamoto,T.et al: "Human prion disease and human prion protein disease." Curr Topics Microbiol Immunol. 207. 27-34 (1996)

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      1996 Annual Research Report
  • [Publications] Furukawa,H.,et al: "A Japapse case of Creutzfeldt-Jakob disease with a point mutation in the prion protein gene at codon 210." J Neurol Sci. 141. 120-122 (1996)

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      1996 Annual Research Report
  • [Publications] Tateishi,J.,et al: "Immunohistochemical evaluation of Creutzfeldt-Jakob disease with reference to the type PrPres deposition." Clin Neuropathol. 15. 358-360 (1996)

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      1996 Annual Research Report
  • [Publications] Nishimura,T.,et al: "Application of IL-12 to antitumor cytokine and gene therapy." Cancer Chemother Pharmacol. 38(Suppl). S27-S34 (1996)

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      1996 Annual Research Report
  • [Publications] Mizuki,N.,et al: "Isolation of cDNA and genomic clones of a humman Ras-related GTP-binding protein gene and its chromosomal localization to the long arm of chromosome7,7q36." Genomics. 34. 114-118 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kajiwara,K.,et al: "Molecular characterization of seizure-related genes isolated by differential screening" Biochem Biophys Res Commun. 219. 795-799 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ando,A.,et al: "cDNA cloning of the human homologues of the mouse Ke4 and Ke6 genes at the centromeric end of the human MHC region." Genomics. 35. 600-602 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kajiwara,K.,et al: "Cloning of SEZ-12 encoding seizure-related and membrane-bound adhesion protein." Biochem Biophys Res Commun. 222. 144-148 (1996)

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      1996 Annual Research Report
  • [Publications] Miyado,K.,et al: "Decreased expression of a single tropomyosin isoform,TM5/TM30nm,results in reduction in motility of highly metastatic B16-F10 mouse melanoma cells." Biochem Biophys Res Commun. 225. 427-435 (1996)

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      1996 Annual Research Report
  • [Publications] Mizuki,N.,et al: "HLA-C genotyping of patients with Behcet's disease in Japanese population." Human Immunol. 50. 47-53 (1996)

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      1996 Annual Research Report
  • [Publications] Igarashi,H.,et al: "Organization and expression of the mouse MTH1 gene for preventing transversion mutation." J Biol Chem. (in press)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsuzuki,T.,et al: "Targeted disruption of the DNA repair methyltranferase gene renders mice hypersensitive to alkylating agent." Carcinogenesis. 17. 1215-1220 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsuzuki,T.,et al: "Targeted disruption of the Rad51 gene leads to lethality in embryonic mice." Proc Natl Acad Sci USA. 93. 6236-6240 (1996)

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      1996 Annual Research Report
  • [Publications] Sekiguchi,M.,et al: "A unique downregulation of h2-calponin gene expression in Down syndrome:a possible attenuation mechanism for fetal survival by methylation at the CpG island in the trisomic Chromosome 21." J Cancer Res Clin Oncol. 122. 100-206 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kuromitsu,J.,et al: "A unique downregulation of h2-calponin gene expression in Down syndrome:a possible attenuation mechanism for fetal survival by methylation at the CpG island in the trisomic Chromosome 21." Mol and Cell Biol. 17(in press).

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      1996 Annual Research Report
  • [Publications] Okuiziumi,H.,et al: "Linkage map of Syrian hamster with restriction landmark genomic scanning." Mammalian Genome. 8(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Okazaki.Y.,et al: "A genetic linkage map of the syrian hamster and localization of cardiomyopathy locus on chromosome 9qa2.1-b1 using RLGS spot-mapping." Nature Genetics. 13. 87-90 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Pearsall,R.S.,et al: "Absence of imprinting in U2afbpL, a human homologue of the imprinted mouse gene U2afbp-rs." Biochem Biophys Res Comm. 222. 171-177 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takahara,T.,et al: "Dysfunction of the Orleans reeler gene arising from exon skipping due to transposition of a full length copy of an active L1 sequence into the skipped exon." Hum Mol Genet. 5. 989-993 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shibata,H.,et al: "Inactive allele-specific methylation and chromatin structure of the imprinted gene U2afbp-rs on mouse Chromosome 11." Genomics. 248-252 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuda,Y.,et al: "Comparative mapping of the reeler gene human Chromosome 7q22,rat Chromosome 4q11.2,and mouse Chromosome 5 A3-B1." Mammalian Genome. 7. 468-469 (1996)

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      1996 Annual Research Report
  • [Publications] Plass,C.,et al: "Identification of Grf1 on mouse chromosome 9 as an imprinted gene by RLGS-M." Nature Genetics. 14. 106-109 (1996)

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      1996 Annual Research Report
  • [Publications] Takada,S.,et al: "Five candidate genes for hamster cardiomyolpathy were not mapped on the cardiomyopathy locus by FISH asnalysis." DNA Res. 3. 273-276 (1996)

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      1996 Annual Research Report
  • [Publications] Hirotsune,S.,et al: "Construction of high-resolution physical maps from yeast artificial chromosomes using restriction landmark genomic scanning(RLGS):whole chromosome two-dimensional fingerprinting mapping." Genomics. 37. 87-95 (1996)

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      1996 Annual Research Report
  • [Publications] Carninci,P.,et al: "High-efficiency full-lenght cDNA cloning by biotinylated CAP trapper." Genomics. 37. 327-336 (1996)

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      1996 Annual Research Report
  • [Publications] Kohno,K.,et al: "Analysis of amyloid deposition in a transgenic mouse model of homozygous familial amyloidotic polyneuropathy." Am J Pathol. (in press).

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      1996 Annual Research Report
  • [Publications] Maeda,S.: "Mouse models of amyloidoses generated by transgenesis." Amyloid:Int J Exp Clin Invest. 3. 214-215 (1996)

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      1996 Annual Research Report
  • [Publications] Kuratani,S.,et al: "Developmental patterning and evolution of the mammalian viscerocranium enetic insights into comparative morphology." Developmental Dynamics. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshida,M.,et al: "Emx1 and Emx2 functions in development of dorsal telencephalon." Development. 124. 101-111 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsuo,M.,et al: "Otx1 function overlaps with Otx2 in development of mouse forebrain and midbrain." Genes to Cells. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Takemoto,M.,et al: "Metanestin, a glycoprotein with metastasis-associated expression in transitional cell carcinoma of the urinary bladder." Int J Cancer. (in press).

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      1996 Annual Research Report
  • [Publications] Kadomatsu,K.,et al: "Midkine induces the transformation of NIH3T3 cells." Brit J Cancer. (in press).

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      1996 Annual Research Report
  • [Publications] Nakanishi,T.,et al: "Expression of syndecan-1 and 3 during embryogenesis of the central nervous system in relation to binding with midkine." J Biochem. (in press).

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      1996 Annual Research Report
  • [Publications] Toriyama,K.,et al: "Evaluation of heparin-binding growth factors in rescueing morphogenesis of heparitinase-treated embryonic lung explants." Differentiation. (in press).

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      1996 Annual Research Report
  • [Publications] Igakura,T.,et al: "Roles of basigin,a member of the immunoglobulin superfamily,in bahavior as to an irritating odor,lymphocyte response and blood brain barrier." Biochem Biophys Res Common. 224. 33-36 (1996)

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      1996 Annual Research Report
  • [Publications] Ozawa,M.,et al: "Molecular cloning and expression of a mouse α-1,3 fucosyltransferase gene that shows homology with human α-1,3 fucosyltransferase IV gene." J Biochem. 199. 302-308 (1996)

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      1996 Annual Research Report
  • [Publications] Kojima,T.,et al: "Human Ryudocan from endothelial-like cells binds basic fibroblast growth factor,midkine,and tissue factor pathway inhibitor." J Biol Chem. 271. 5914-5920 (1996)

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      1996 Annual Research Report
  • [Publications] Inui,T.,et al: "Solution synthesis of human midkine,a novel heparin binding neurotrophic factor consisting of 121 amino acid residues with five disulphide bonds." J Peptide Sci. 2. 28-39 (1996)

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      1996 Annual Research Report
  • [Publications] Kaname,T.,et al: "The expression of truncated MK in human tumors." Biochem Biophys Res Commun. 219. 256-260 (1996)

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      1996 Annual Research Report
  • [Publications] Koike,C.,et al: "Introduction of α(1,2)-fucosyltransferase and its effect on α-Gal epitopes in transgenic pig." Xenotransplantation. 3. 81-86 (1996)

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      1996 Annual Research Report
  • [Publications] Kaneda,N.,et al: "Stuctural characteristics of heparin-like domain required for interaction of midkine with embryonic neurons." Biochem Biophys Res Commun. 220. 108-112 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kaneda,N.,et al: "Midkine,a heparin-binding growth/differentiation factor,possesses nerve cell adhesion and guidance activity for neurite outgrowth in vitro." J Biochem. 119. 1150-1156 (1996)

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      1996 Annual Research Report
  • [Publications] Muramatsu,H.,et al: "Enzyme-linked immunoassay of midkine and its application in evaluating midkine levels in the developing mouse brain and in sera from patients with hepatocellular carcinome." J Biochem. 119. 1171-1175 (1996)

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      1996 Annual Research Report
  • [Publications] Adachi,Y.,et al: "Midkine as a novel target gene for Wilms tumor suppressor(WTI)." Oncogene. 13. 2197-2203 (1996)

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      1996 Annual Research Report
  • [Publications] Matsuda,Y.,et al: "Limited proteolysis by chymotrypsin of midkine and inhibition by heparin binding." Biochem Biophys Res Commun. 228. 176-181 (1996)

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      1996 Annual Research Report
  • [Publications] Itohara,S.,et al: "Gene Targeting and New Developments in Neurobiology" Japan Scientific Societies Press, 253 (1996)

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      1996 Annual Research Report
  • [Publications] Yamaguchi, H., et al.: "Dopamine D2 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituitary." Genes to Cells. in press.

    • Related Report
      1995 Annual Research Report
  • [Publications] Gondo, Y., et al.: "A novel positive detection system of in vivo mutations in rpsL(strA)transgenic mice." Mutation Res. in press.

    • Related Report
      1995 Annual Research Report
  • [Publications] Masu, M., et al.: "Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene." Cell. 80. 757-765 (1995)

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      1995 Annual Research Report
  • [Publications] Shimano, H., et al.: "Inhibition of diet-induced atheroma formation in transgenic mice expressing apolipoprotein E in the arterial wall." J Clin Invest. 95. 469-476 (1995)

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      1995 Annual Research Report
  • [Publications] Honda, H., et al.: "Increased tyrosine-phosphorylation of 55KDa proteins in beta-actin/Tec transgenic mice." Biochem Biophys Res Commun. 206. 287-293 (1995)

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      1995 Annual Research Report
  • [Publications] Tamura, H., et al.: "Opaque eyes developed in transgenic mice with T-cell receptor δ gene." Invest Ophthalmol Vis Sci. 36. 467-477 (1995)

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      1995 Annual Research Report
  • [Publications] Komano, H., et al: "Homeostatic regulation of intestinal epithelia by intraepithelial γδ T cells." Proc Natl Acad Sci USA. 92. 6147-6151 (1995)

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      1995 Annual Research Report
  • [Publications] Gomi, H., et al.: "Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions." Neuron. 14. 29-41 (1995)

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      1995 Annual Research Report
  • [Publications] Emoto, M., et al.: "Mice dificient in γδ T cells are resistant to lethal infection with Salmonella choleraesuis." Infect Immun. 63. 3736-3738 (1995)

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      1995 Annual Research Report
  • [Publications] Nishimura, H., et al.: "The role of γδ T cells in priming macrophages to produce tumor necrosis factor-α." Eur Immunol. 25. 1465-1468 (1995)

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      1995 Annual Research Report
  • [Publications] Nakane, H., et al.: "High incidence of UVB-or chemical carcinogen-induced skin tumorigenesis in mice lacking the xerodema pigmentosum group A(XPA)gene." Nature. in press.

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      1995 Annual Research Report
  • [Publications] Kaneda, Y., et al.: "The recycling of synaptic vesicle membrane components. “Protein Kinesis: The Dynamics of Protein Trafficking and Stability"" Cold Spring Harbor Symp. Quant. Biol. 60(in press).

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      1995 Annual Research Report
  • [Publications] Mann, M. J., et al.: "Genetic engineering of vein grafts resistant to atherosclerosis." Proc Natl Acad Sci USA. 92. 4502-4506 (1995)

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      1995 Annual Research Report
  • [Publications] von der Leyen, H. E., et al.: "Gene therapy inhibiting neointimal vascular lesion: In vivo transfer of endothelial cell nitric oxide synthase gene." Proc Natl Acad Sci USA. 92. 1137-1141 (1995)

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      1995 Annual Research Report
  • [Publications] Kaneda. Y., et al.: "Increased wxpression of DNA cointroduced with nuckear protein in adult rat liver." J Mol Med. 73. 289-297 (1995)

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      1995 Annual Research Report
  • [Publications] Mizuki, N., et al.: "Isolation of cDNA and genomic clones of a human Ras-related GTP-binding protein gene and its choromosomal localization to the long arm of choromosome 7, 7q36." Genomics. in press.

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsai, HJ., et al.: "Initiation of the transgenic lacZ gene expression in medaka(Oryzias latipes)embryos." Mol Mar Biol Biotechnol. 4. 1-9 (1995)

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      1995 Annual Research Report
  • [Publications] Naruse, T., et al.: "Cloned PLT cells recognize the forth,fifth and sixth hypervariable regions at amino acid positions 65 to 87 of DPB1 molecule." Human Immunol. 42. 123-130 (1995)

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      1995 Annual Research Report
  • [Publications] Kajiwara, K., et al.: "Cloning and characterization of pentylenetetrazol-related cDNA, PTZ-17." Brain Res. 671. 170-174 (1995)

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      1995 Annual Research Report
  • [Publications] Cai, J-P., et al.: "cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nucleotides." Carcinogenesis. 16. 2343-2350 (1995)

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      1995 Annual Research Report
  • [Publications] Kakuma, T., et al.: "Mouse MTH1 protein with 8-Oxo-7,8-dihydro-2′-deoxyguanosine5′-triphatase activity that prevents transversion mutation." J Biological Chem. 270. 2542-2548 (1995)

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      1995 Annual Research Report
  • [Publications] Rancourt, D. E., et al.: "Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation." Genes Dev. 9. 108-122 (1995)

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      1995 Annual Research Report
  • [Publications] Kuromitsu, J., et al.: "Programmed alterations of DNA methylation at CpG islands during blastformation of peripheral blood lymphocytes." DNA Res. in press.

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      1995 Annual Research Report
  • [Publications] Plass, C., et al.: "Comparative analysis of mouse NotI Iinking clones with mouse and human genomic sequences and transcripts." DNA Res. 2. 27-35 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirotsune, S., et al.: "The reeler gene encodes a protein with EGF-like motif expressed by pioneer neurons." Nature Genetics. 10. 77-83 (1995)

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      1995 Annual Research Report
  • [Publications] Latham, K., et al.: "Stage-specific induction and regulation by genomic imprinitng of mouse U2bpaf-rs gene during preimplantation development." Developmental Biology. 168. 670-676 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okazaki, Y., et al.: "Direct detection and isolation of RLGS spot DNA marker tightly linked to a specific trait using RLGS spot-bombing method." Proc Natl Acad Sci USA. 92. 5610-5614 (1995)

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      1995 Annual Research Report
  • [Publications] Ohsumi, T., et al.: "Loss of heterozygosity in chromosomes 1, 5, 7and13 in mouse hepatoma detected by systematic genome-wide scanning RLGS genetic map." Biochem Biophys Res Commun. 212. 632-639 (1995)

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      1995 Annual Research Report
  • [Publications] Kalcheva, I., et al.: "Comparative mapping of the imprinted U2afbpL gene on mouse chromosome11 and human chromosome5." Cytogenet Cell grenet. 68. 19-24 (1995)

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      1995 Annual Research Report
  • [Publications] Okazaki, Y, et al.: "Amultiplex procduction system of RLGS gel-A new version of restriction landmark genomic scanning method(RLGS Ver1, 8)." Electrophoresis. 16. 197-202 (1995)

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      1995 Annual Research Report
  • [Publications] Ohsumi, T, et al.: "RLGS spot cloning method." Electrophoresis. 16. 203-209 (1995)

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      1995 Annual Research Report
  • [Publications] Shibata, H., et al.: "Systematic screening of endogenous imprinted genes using RLGS and identification of a new imprinted gene U2af binding protein related sequence." Electrophoresis. 16. 210-217 (1995)

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      1995 Annual Research Report
  • [Publications] Watanabe, S., et al.: "Accessibilitey to tissue-specific genes from methylantion profiles of mouse brain genomic DNA." Electrophoresis. 16. 218-226 (1995)

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      1995 Annual Research Report
  • [Publications] Okuizumi, H., et al.: "Genetic mapping of restriction landmark senomic scanning(RLGS)loci in the mouse." Electrophoresis. 16. 233-240 (1995)

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      1995 Annual Research Report
  • [Publications] Okuizumi, H., et al.: "A single gel analysis of 573 dominant and codominant restriction landmark genomic scanning(RLGS)loci in interspecific backcross progeny." Electrophoresis. 16. 253-260 (1995)

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      1995 Annual Research Report
  • [Publications] Horie, K., et al.: "A replacement vector us ed to introduce subtle mutaions into mouse genes." Gene. in press.

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      1995 Annual Research Report
  • [Publications] Kato, G. et al.: "Novel phosphory lation at a mitotic site, serine 75,in human pp60^<c-src> from unsynchronized human tumor cells having a spherical morphology." Biochem Biophys Res Commun. 216. 619-629 (1995)

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      1995 Annual Research Report
  • [Publications] Wei, S., et al.: "Studies on the metabolism of retinol and retinol-binding protein in transthyretin-deficient mice produced by homologous recombi-nation." J Biol Chem. 270. 866-870 (1995)

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      1995 Annual Research Report
  • [Publications] Matsuo. I., et al.: "Mouse Ot×2 functions in the formation and patteming of rostral head." Gene Dev. 9. 2646-2658 (1995)

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      1995 Annual Research Report
  • [Publications] Miyauchi, T., et al.: "Structure of the mouse basigin gene,a unique member of the immunoglobulin superfamily." J Biochem. in press.

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      1995 Annual Research Report
  • [Publications] Masuda, K., et al.: "Functional rescue of photoreceptos from the damaging effects of constant light by survival-promoting factors in the rat." Invest Ophtalmol Vis Sci. in press.

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      1995 Annual Research Report
  • [Publications] Obama, H., et al.: "A transgenic mouse line with α-1,3/4 fucosyltransferase cDNA:production and characteristics." Glycoconjugate J. 12. 795-801 (1995)

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      1995 Annual Research Report
  • [Publications] Yu, S., et al.: "cDNA cloning and sequence analysis of a novel calcium binding protein with oligoproline motif" Cell Struct Funct. 20. 263-268 (1995)

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      1995 Annual Research Report
  • [Publications] Kojima, S., et al.: "Midkine enhances fibrinolytic activity of bovine endothelial cells." J Biol Chem. 270. 9590-9596 (1995)

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      1995 Annual Research Report
  • [Publications] Naved, AF., et al.: "CBP-140,a novel endoplasmic reticulum resident Ca2+-binding protein with a carboxy terminal NDEL sequence showed partial homology with 70kDa heat shock protein(hsp70)." Cell Struct Funct. 20. 133-141 (1995)

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      1995 Annual Research Report
  • [Publications] Sudou, A., et al.: "Lewis X structure increases cell substratum adhesion in L cells." J Biochem. 117. 271-275 (1995)

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      1995 Annual Research Report
  • [Publications] Mitsiadis, T. A., et al.: "Midkine(MK),a heparin-binding growth/differentiation factor,is regulated by retinoic acid and epithelial-mesenchymal interactions in the developing mouse tooth, and affects cell proliferation and morphogenesis." J Cell Biol. 129. 267-281 (1995)

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      1995 Annual Research Report
  • [Publications] Mitsiadis, T. A., et al.: "Expression of the heparin-binding cytokines,midkine(MK)and HB-GAM(pleiotrophin)is associated with epithelial-mesenchymal interactions during fetal development andorganogenesis." Development. 121. 37-51 (1995)

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      1995 Annual Research Report
  • [Publications] Tsunematsu,S.,et al.: "Hepatic tumors induced by carbon tetrachloride in transgenic mice carrying human c-H-ras proto-oncogene without mutations." Int J Cancer. 59. 554-559 (1994)

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      1994 Annual Research Report
  • [Publications] Sato,M.,et al.: "Naive T cells can mediate delayed-type hypersensitivity response in Tcell receptor transgenic mice." Eur J Immunol. 24. 1512-1516 (1994)

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      1994 Annual Research Report
  • [Publications] Lafaille,JJ.,et al.: "High incidence of spontaneous autoimmune encephalomyelitis in immuno-deficient anti-myelin basic protein Tcell receptor trasgenic mice." Cell. 78. 399-408 (1994)

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      1994 Annual Research Report
  • [Publications] Gondo,Y.,et al.: "Gene replacement of the p53 gene with the lacZ gene in mouse embryonic stem cells and mice by using two steps of homologous recombination." Biochem Biophys Res Commun. 202. 830-837 (1994)

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      1994 Annual Research Report
  • [Publications] Doi,ST.,et al.: "Tissue-specific tumorigenesis Induced by Dimethylbenzanthracene in transgenic mice carrying human c-Ha-ras proto-oncogenes." Jpn J Can Res. 85. 801-807 (1994)

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      1994 Annual Research Report
  • [Publications] Miyado,K.,et al.: "Isolation of a yeast cDNA clone that encodes a novel trans-membrane protein having a c-terminal highly basic region." Biochem Biophys Res Commun. 199. 1363-1371 (1994)

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      1994 Annual Research Report
  • [Publications] Nada,S.,et al.: "Identification of major tyrosine-phosphorylatedproteins in Csk-deficient cells." Oncogene. 9. 3571-3578 (1994)

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      1994 Annual Research Report
  • [Publications] Umemori,H.,et al.: "Initial events of myelination involve Fyn tyrosine kinase signalling." Nature. 367. 572-576 (1994)

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      1994 Annual Research Report
  • [Publications] Kubo,S.,et al.: "A novel form of self tolerance dictated in the thymus of transgenic mice with autoreactive TCRα and βchain genes." Int Immunol. 6. 593-602 (1994)

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      1994 Annual Research Report
  • [Publications] Hashimoto,N.,et al.: "Parthenogenetic activation of oocytes,but normal spermatogenesis and somatic cell growth,by c-mos-deficiency in mice." Nature. 370. 68-70 (1994)

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      1994 Annual Research Report
  • [Publications] Yagi,T.,et al.: "Fyn expression during neurogenesis in mouse embryos." Oncogene. 9. 2433-2440 (1994)

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      1994 Annual Research Report
  • [Publications] Tanaka,N.,et al.: "Cellular commitment to oncogene-induced transformation or apoptosisis dependent on the transcription factor IRF-1." Cell. 77. 829-839 (1994)

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      1994 Annual Research Report
  • [Publications] Kohmura,N.,et al.: "A novel non-receptor tyrosine kinase,srm;cloning and targeted disruption." Mol Cell Biol. 14. 6915-6925 (1994)

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      1994 Annual Research Report
  • [Publications] Ishizaki,K.,et al.: "Increased UV-induced SCEs in p53-deficient mouse cells." Int J Cancer. 58. 254-257 (1994)

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      1994 Annual Research Report
  • [Publications] Tamemoto,H.,et al.: "Targeted disruption of the insulin receptor substrate-1 gene results in insulin resistance and growth retardation." Nature. 372. 182-186 (1994)

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      1994 Annual Research Report
  • [Publications] Gomi,H.,et al.: "Prion protein (PrP) is not involved in the pathogenesis of spongiform encephalopathy in zitter rats." Neurosci Lett. 166. 171-174 (1994)

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      1994 Annual Research Report
  • [Publications] Takahama,Y.,et al.: "Entry of CD4^-CD8^- immature thymocytes into the CD4/CD8 developmental pathway is controlled by thymidine kinase signals that can be provided throught Tcell receptor components." Int Immunol. 6. 1505-1514 (1994)

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      1994 Annual Research Report
  • [Publications] Morishita,R.,et al.: "Intimal hyperplasia after vascular injury is inhibited by antisense cdc2 kinase oligonucleotides." J Clin Invest. 93. 1458-1464 (1994)

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      1994 Annual Research Report
  • [Publications] Tomita,N.,et al.: "A novel gene transfer technique mediated by HVJ(Sendai virus),nuclear protein and liposomes." Cancer Diagno Prev. 18. 485-491 (1994)

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      1994 Annual Research Report
  • [Publications] Naora,H.,et al.: "Transgenic mouse model of hemifacial microsomia:cloning and characterization of insertional mutation region on Chromosome 10." Genomics. 23. 515-519 (1994)

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      1994 Annual Research Report
  • [Publications] Takagi,S.,et al.: "An efficient expression vector for transgenic medaka construction." Mol Marine Biol Biotechnol. 3. 192-199 (1994)

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      1994 Annual Research Report
  • [Publications] Okuizumi,H.,et al.: "Application of the RLGS method to large-size genomes using restriction trapper." DNA Research. 1. 99-102 (1994)

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      1994 Annual Research Report
  • [Publications] Sasaki,N.,et al.: "The gene responsible for LEC hepatitis,located on rat chromosome 16,is the homolog to the human Wilson disease gene." Biochem Biophys Res Commun. 202. 512-518 (1994)

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      1994 Annual Research Report
  • [Publications] Kalcheva,I.,et al.: "Comparative mapping of the imprinted U2afbpL gene on mouse chromosome II and human chromosome 5." Cytogenet Cell Genet. 68. 19-24 (1995)

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      1994 Annual Research Report
  • [Publications] Maki,K.,et al.: "Targeted pituitary tumorigenesis using the human thyrotropin β-subunit chain promoter in trnasgenic mice." J Mol Cell Endocrinol. 105. 147-154 (1994)

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      1994 Annual Research Report
  • [Publications] Kawai,J.,et al.: "Comparison of DNA methylation patterns among mouse cell lines by restriction landmark genomic scanning." Mol Cell Biol. 14. 7421-7427 (1994)

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      1994 Annual Research Report
  • [Publications] Imoto,H.,et al.: "Direct determination of NotI cleavage sites inthe genomic DNA of adult mouse kidney and human trphoblast using whole range restriction landmark genomic scanning." DNA Res. 1. 239-243 (1994)

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  • [Publications] Hayashizaki,Y.et al.: "A genetic linkage map of the mouse using Restriction Landmark Genomic Scanning(RLGS)." Genetics. 138. 1207-1238 (1994)

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      1994 Annual Research Report
  • [Publications] Tada,M.,et al.: "Localization of mouse imprinted gene U2afbp-rsto A3.2-4 band of Chromosome 11 by FISH." Mammalian Genome. 5. 655-657 (1994)

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      1994 Annual Research Report
  • [Publications] Hirotsune,S.,et al.: "Spot mapping onthe standard profile of restriction landmark genomic scanning(RLGS) of sorted chromosome 20 using methylation-insensitive enzyme." Genomics. 24. 593-596 (1994)

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      1994 Annual Research Report
  • [Publications] Hayashizaki,Y.: "Systematic screening of endogenous imprinted genes using RLGS and identification of a new imprinted gene U2af binding protein related" sequence." RIKEN Review. 6. 41-43 (1994)

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      1994 Annual Research Report
  • [Publications] Hayashizaki,Y.,et al.: "Identification of an imprinted U2af binding protein related sequence on mouse chromosome 11 using the RLGS method." Nature Gen. 6. 33-40 (1994)

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      1994 Annual Research Report
  • [Publications] Horie,K.,et al.: "Structures of replacement vectors for efficient gene targeting." J Biochem. 115. 477-485 (1994)

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      1994 Annual Research Report
  • [Publications] Nagata,Y.,et al.: "A6-kb upstream region of the human trasthyretin gene can direct developmental,tissue-specific and quantitatively normal expression in transgenic mouse." J Biochem. 117. 169-175 (1994)

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      1994 Annual Research Report
  • [Publications] 勝木元也: "Molecular Medicine(臨時増刊)マニュアル疾患モデルマウス" 中山書店, 397 (1994)

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  • [Publications] Imai,E.,et al.: "Extracellular Matrix in the Kidney" Basel,Karger, 226 (1994)

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      1994 Annual Research Report
  • [Publications] Akiyama,M. Katsuki,M.,et al.: "Lymphocyte infiltration of the skin in transgenic mice carrying the human interleukin-2 gene." Arch Dermatol Res. 285. 379-384 (1993)

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      1993 Annual Research Report
  • [Publications] Takaori,K. Katsuki,M.,et al.: "Biochemical characteristics of human renin expressed in transgenic mice." Clinical Science. 84. 21-29 (1993)

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

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      1993 Annual Research Report
  • [Publications] Miyado,K. Katsuki,M.,et al.: "Isolation of a yeast cDNA clone that encodes a novel transmembrane protein having a c-terminal highly basic region." Biochem Biophys Res Commun. in press. (1994)

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      1993 Annual Research Report
  • [Publications] Imoto,S. Aizawa,S.,et al: "Regulation of class II MHC gene expression by the inducible antisense RNA in transgenic mice." Anal Biochem. 210. 231-234 (1993)

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      1993 Annual Research Report
  • [Publications] Furuta,Y. Aizawa,S.,et al: "Degeneration of skeletal and cardiac muscles in c-myb transgenic mice." Transgenic Res. 2. 199-207 (1993)

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      1993 Annual Research Report
  • [Publications] Yagi,T. Aizawa,S.et al.: "A novel negative selection for homologous recombinants using diphtheria toxin A a fragment gene." Anal Biochem. 214. 77-86 (1993)

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      1993 Annual Research Report
  • [Publications] Yagi,T. Aizawa,S.et al.: "A novel ES cell line,TT2,with high germline-differentiatin potency." Anal Biochem. 214. 70-76 (1993)

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      1993 Annual Research Report
  • [Publications] Yagi,T. Aizawa,S.,et al: "A novel negative selection for homologous recombinants using diphteria toxin A fragment gene." Anal Biochem. 214. 379-384 (1993)

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      1993 Annual Research Report
  • [Publications] Yagi,T. Aizawa,S.: "A novel ES cell line,TT2,with high germline-differentiating potency." Anal Biochem. 214. 70-76 (1993)

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      1993 Annual Research Report
  • [Publications] Yagi,T. Aizawa,S. et al.: "Regional localization of Fyn in adult brain;studies with mice in which fyn gene was replaced by lacZ." Oncogene. 8. 3343-3351 (1993)

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      1993 Annual Research Report
  • [Publications] Tsukada,T. Aizawa,S. et al.: "Enhanced proliferative potential in culture of cells from p53-deficient mice." Oncogene. 8. 3313-3322 (1993)

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      1993 Annual Research Report
  • [Publications] Yagi,T. Aizawa,S.et al.: "A role for Fin tyrosine kinase in the suckling behavior of neonatal mice." Nature. 366. 742-745 (1993)

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      1993 Annual Research Report
  • [Publications] Itohara,S.et al.: "T-cell receptor delta gene mutant mice:Independent generation of gamma delta T cells and programmed rearrangements of gamma delta TCR genes." Cell. 72. 337-348 (1993)

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      1993 Annual Research Report
  • [Publications] Gomi.H. Itohara.S.et al.: "Prion protein(PrP)is not involved in the pathogenesis of spongiform encephalopathy in zitter rats." Neuroscience Letters. (in press). (1994)

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      1993 Annual Research Report
  • [Publications] Isaka,Y. Kaneda,Y.et al.: "Glomerulosclerosis induced by in vivo transfection with TGF beta-or PDGF gene into rat kidney." J Clin Invest. (in press). (1994)

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      1993 Annual Research Report
  • [Publications] Morishita,R. Kaneda,Y.: "In vivo gene transfer into intact blood vessels by HVJ method." Circulation. (in press). (1994)

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      1993 Annual Research Report
  • [Publications] Tomita,N. Kaneda,Y.et al.: "A novel gene transfer technique mediated by HVJ (Sendai Virus),nuclear protein and liposomes." Cancer Detection and Prevention. in press. (1994)

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      1993 Annual Research Report
  • [Publications] Morishita,R. Kaneda,Y.et al.: "Intimal hyperplasia after vascular injury is inhibited by antisence CDK2 kinase oligonucleotide." J Clin Invest. in press. (1994)

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      1993 Annual Research Report
  • [Publications] Kaneda,Y. et al.: "The analysis of 40 kDa nuclear protein,p40,in interphase cells and mitotic cells." J Cell Sci. 106. 741-748 (1993)

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      1993 Annual Research Report
  • [Publications] Morishita,R. Kaneda,Y.et al.: "Single intraluminal delivery of antisense cdc2 kinase and proliferating-cell nuclear antigen oligonucleotides results in chronic inhibition of neointimal hyperplasia." Proc Natl.Acad Sci USA. 90. 8474-8478 (1993)

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      1993 Annual Research Report
  • [Publications] Uchiyama,A. Kaneda,Y. et al.: "Transfection of interleukin-2 gene into human melanoma cells augments cellular immune response." Cancer Res.53. 949-952 (1993)

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      1993 Annual Research Report
  • [Publications] Tomita,N. Kaneda,Y.et al.: "Hypertensive rats produced by in vivo introduction of the human renin gene." Circulation Res. 73. 898-905 (1993)

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      1993 Annual Research Report
  • [Publications] Morishita,R. Kaneda,Y.et al.: "Novel in vitro gene transfer method for study of local modulators in vascular smooth muscle cells." Hypertension. 21. 894-899 (1993)

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      1993 Annual Research Report
  • [Publications] Morishita,R. Kaneda,Y.et al.: "Novel and effective gene transfer technique for study of vascular renin angiotensin system." J Clin Invest. 91. 2580-2585 (1993)

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      1993 Annual Research Report
  • [Publications] Takagi,S. Kimura,M. et al.: "Direct sequencing of PCR products using unlabelled primers." BioTechniques. 14. 218-221 (1993)

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      1993 Annual Research Report
  • [Publications] Hayashizaki,Y. Katsuki,M. et al.: "Restriction landmark genomic scanning and its various application." Electrophoresis. 14. 251-258 (1993)

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      1993 Annual Research Report
  • [Publications] Hirotsune,S. Hayashizaki,Y.et al.: "Molecular cloning of polymorphoic markers on RLGS gel using the spot target cloning method." Biochem Biophys Res Commun. 194. 1406-1412

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      1993 Annual Research Report
  • [Publications] Nagai,H.Hayashizaki,Y.et al: "Genomic analysis of human hepatocellular carcinomas using restriction landmark genomic scanning." Cancer Detect. Prevention. 17. 399-404 (1993)

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      1993 Annual Research Report
  • [Publications] Kawai,J.Hayashizaki,Y.et al.: "Methylation profile of genomic DNA mouse developmental brain detected by restriction landmark genomic scanning(RLGS) method." Nucl Acid Res. 21. 5604-5608 (1993)

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      1993 Annual Research Report
  • [Publications] 勝木元也: "神経疾患の分子医学 「高次神経機能を遺伝子から視る」" 羊土社, 148 (1993)

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      1993 Annual Research Report
  • [Publications] 前田秀一郎: "神経疾患の分子医学 「優性遺伝病、家族性アミロイドポリニューロパチーのモデルマウスの作出」" 羊土社, 148 (1993)

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      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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