1996 年度実績報告書

標的遺伝子組換えによる生体機能の研究

研究課題

研究課題/領域番号	05275101
研究機関	東京大学
研究代表者	勝木元也東京大学, 医科学研究所, 教授 (20051732)
研究分担者	野田哲生 (財)癌研究会癌研究所, 部長 (10183550) 中辻憲夫国立遺伝学研究所, 教授 (80237312) 近藤寿人大阪大学, 細胞生体工学センター, 教授 (70127083) 相沢慎一熊本大学医学部, 遺伝発生研究所, 教授 (60073011) 山村研一熊本大学医学部, 遺伝発生研究所, 教授 (90115197)
キーワード	標的遺伝子組換え / ジーンターゲッティング / ドーパミン受容体 / H-ras / N-ras / K-ras / セロトニン受容体 / バイオサイエンス
研究概要	本研究は標的遺伝子組換え法を用い、突然変異マウスの作成により、生体の形質転換を通して、現代のバイオサイエンスの大きな課題の一つである個体レベルでの遺伝子機能の研究が目的である。本班は、2つの計画研究と公募研究とからなり、班員の研究を評価し、班員相互の協力を励まし、方法や資材において共有できるよう指導する役割を担っている。目的を達成するために、ニュースレターの作製と配布、幹事会の開催、班員の研究現場への相互訪問、および班会議を行った。本研究は、動物の個体を対象とすることから、技術はもちろん、施設や費用の点で負担が大きく、いつでも、どこでも、実施可能であるとはいえないところに問題がある。そこで本邦では将来においては専門的実施施設を数ヵ所に設定する必要性が論じられた。この方向に沿って総括班から重点配分として、東大、熊大、および癌研に配分され、その準備が行われた。またそれぞれ多くの標的組換えマウス(ジーンターゲッティングマウス)が作成された。本研究によって得られた遺伝子標的マウスを列挙すれば、セロトニン受容体、ドーパミン受容体、P53、H-ras、N-ras、K-ras、などすでに200種を越えている。これらのマウスの作成を通して、本邦での本研究の広がりと重要性とが確認された。

研究成果
(54件)

すべてその他

すべて文献書誌 (54件)

[文献書誌] Suda,Y.,et al.: "Otx1 function overlaps with Otx2 in development of mouse forebrain and midbrain." Genes to Cells. (in press)
[文献書誌] Nakayama,T.,et al: "Fracture healing is a process independent of p53 function." Biochem Biophys Res Commun. (in press)
[文献書誌] Yasunaga,M.,et al: "Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor." J Cell Biol. 132. 1-9 (1996)
[文献書誌] Ilic,D.,et al: "Impairment of mobility in endodermal cells by FAK-deficiency." Exp Cell Res. 222. 298-303 (1996)
[文献書誌] Kanazawa,S.,et al: "Cooperation of p59 fyn and p125FAK in Development of CD4+CD8+Thymocytes." Blood. 87. 865-870 (1996)
[文献書誌] Nanazawa,S.,et al: "Impaired development of CD4+CD8+thymocytes by csk-“knoch-in"into fyn locus." Oncogene. 13. 199-204 (1996)
[文献書誌] Kato,M.V.,et al: "A follistatin-like gene,mac 25,may act as a growth suppressor of osteosarcama cells." Oncogene. 12. 1361-1364 (1996)
[文献書誌] Ishizaki,K.,et al: "UV-induced mutatiioons of supF gene on a shuttle vector plasmid in p53-deficentmouse cells are qualitatively defferent from those in wild-type cells." Mut Res. 364. 43-49 (1996)
[文献書誌] Enokido,Y.,et al: "p-53 involves cytosine arabinoside-induced apoptosis in cultured cerebellar granule neurons" Neurosci Left. 203. 1-4 (1996)
[文献書誌] Yamauchi.T.,et al: "Insulin signalling and actions in the muscles and livers of insulin-resistant,insulin receptor substrate 1-deficient mice." Mol Cellr Biol. 16. 3074-3084 (1996)
[文献書誌] Vuori,K.,et al: "Induction of p130^<cas> signaling complex formation upon integrin-mediated cell adhesion:a role for src family kinase." Mol Cellr Biol. 16. 2606-2613 (1996)
[文献書誌] Enokido,Y.,et al: "Involvement of p53 in DNA stand break-induced apoptosis in postmitotic CNS neurons." Eur J Neurosci. 8. 1812-1821 (1996)
[文献書誌] Shimoji,M.,et al: "Application of primary hepatocytes from p53-knockout mice for studies of expression of Cyp3a" J.Biochem. 120. 42-48 (1996)
[文献書誌] Hamaguchi,I.,et al: "Analysis of CSK homologous kinase(CHK/HYL)in hematopoiesis by utilizing gene knockout mice." Biochem Biophys Res Commun. 224. 172-179 (1996)
[文献書誌] Tanaka,N.,et al: "Cooperation of the tumour suppressors IRF-1 and p53 in response to DNA damage." Nature. 382. 816-818 (1996)
[文献書誌] Hamasaki,K.,et al: "Src kinase plays an essential role in integrin-mediated tyrosine phosphorylation of Crk-associated substrate p130^<Cas>." Biochem Biophys Res Commun. 222. 338-343 (1996)
[文献書誌] Kutsuwada,T.,et al: "Impairment of suckling response,trigeminal neuronal pattern formation and hippocampal LTD in NMDA receptor ε2 subunit mutant mice." Neuron. 16. 333-344 (1996)
[文献書誌] Yoshida,M.,et al: "Emx1 and Emxd2 functions in development of dorsal telencephalon." Development. 122. 4-9 (1996)
[文献書誌] Takamiya,K.,et al: "Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous sustem." Proc Natl Acad Sci USA. 93. 10662-10667 (1996)
[文献書誌] Araki,K.,et al: "Meiotic abnoralities of c-mos knockout mouse oocytes:Activation after first meiosis or entrance into third meiotic metaphase." Biol Rep. 55. 1315-1324 (1996)
[文献書誌] 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)
[文献書誌] Yokoi,M.,et al: "Impariment of hippocampal mossy fiber LTD in mice lacking mGluR2." Scienc. 273. 645-647 (1996)
[文献書誌] Kato,T.,et al: "Inactivation of hepatitis C virus cDNA transgene by hypermethylation intransgenic mice." Arch Virol. 141. 951-958 (1996)
[文献書誌] Inoue,R.,et al: "Rare activation of the human c-Ha-rastransgene of mice in hemangioendothelial sarcomas and liver tumors induced by Glu-P-1." Jpn J Cancer Res. 87. 583-588 (1996)
[文献書誌] 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)
[文献書誌] Li,Y.,et al: "Establishiment of transgenic mice carrying human fetus-specific CYP3A7." Arch Biochem Biophys. 329. 235-240 (1996)
[文献書誌] Gondo,Y.,et al: "A novel positive detection system of in vivo mutations in rpsL(strA)transgenic mice." Mutation Res. 360. 1-14 (1996)
[文献書誌] Norimura,T.,et al: "p53-dependent apoptosis suppresses radeation-induced teratogenesis." Nature Medicine. 2. 577-580 (1996)
[文献書誌] 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)
[文献書誌] Tokita,Y.,et al: "Characterization of excitatory amino acid neurotoxcity in N-methy1-D-aspartate receptor-deficient mouse cortical neuronal cells." Eur J Neurosci. 8. 69-78 (1996)
[文献書誌] Kitamoto.T.,et al: "Humanized prion protein knock-in by Cer-induced site-specific recombination in the mouse." Biochem Biopys Res Commun. 222. 742-747 (1996)
[文献書誌] Tsuzuki,T.,et al: "Targeted disruption of the DNA repair methyltransferase gene renders mice hypersensitive to alkylating agent." Carcinogenesis. 17. 1215-1220 (1996)
[文献書誌] Shibata,H.,et al: "Inactive allele-specific methylation and chromatin structure of the imprinted gene U2afbp-rs1 on mouse Chromosome 11." Genomics. 35. 248-252 (1996)
[文献書誌] Higashi,Y.,et al: "Impairment of T cell development in δEF1 mutant mice." J Exp Med. (in press)
[文献書誌] Shimono,A.,et al: "Requirement of N-myc protein down-regulation for neuronal differentiation in the spinal cord." Dev Growth Differ. 38. 707-717 (1996)
[文献書誌] Sekido,R.,et at: "Organization of the gene encoding transcriptional repressor δEF1 and cross-species conservation of encoded protein domains." Gene. 173. 227-232 (1996)
[文献書誌] Shoji,H.,et al: "Regionalized expression of the Dbx family homeobox genes in the embryonic CNS of the mouse." Mech Dev. 56. 25-39 (1996)
[文献書誌] Watanabe,M.,et al: "Gene transfection of mouse primordial germ cells in vitro and analysis of their survival and growth control." Exp Cell Res. (in press).
[文献書誌] Kawase,E.,et al: "A combination of Buffalo rat liver cell-conditioned medium,forskolin and membrane-bound stem cell factor stimulates rapid proliferation of mouse primordial germ cells in vitro similar to that in vivo." Devel Growth Differ. 38. 315-322 (1996)
[文献書誌] Koshimizu,U.,et al: "Functional requirement of gp130-mediated signaling for growth and survival of mouse primordial germ cells in vitro and derivation of embryonic germ(EG)cells." Dev. 122. 1235-1242 (1996)
[文献書誌] Ohkubo,Y.,et al: "Autonomous regulation of proliferation and growth arrest in mouse primordial germ cells studied by mixed and clonal cultures." Exp Cell Res. 222. 291-297 (1996)
[文献書誌] Nishi,M.,et al: "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking nociceptin/orphaninFQ receptor." EMBOJ. (in press)
[文献書誌] Matsumoto,M.,et al: "Ataxia and epileptic seizure in mice lacking type 1 inositol 1,4,5-trisphophate receptor." Nature. 379. 168-171 (1996)
[文献書誌] Sakaguchi,S.,et al: "Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene." Nature. 380. 528-531 (1996)
[文献書誌] Takeshima,H.,et al: "Generation and characterization of mutant mice lacking ryanodine receptor type3." J Biol Chem. 271. 19649 (1996)
[文献書誌] Nagata,A.,et al: "G protein-coupled cholecystokinin-B/gastrin receptors are responsible for physiological cell growth of the stomach mucosa in vivo." Proc Natl Acad Sci USA. 93. 11825-11830 (1996)
[文献書誌] Shimada,A.,et al: "Immune response to heat-shock protein correlates with induction of insulitis in I-Eαd transgenic NOD mice" Diabetes. 45. 165-169 (1996)
[文献書誌] Kaname,T.,et al: "The expression of trunccated MKin human tumors." Biochem Biophys Res Commun. 219. 256-260 (1996)
[文献書誌] Niwa,H.,et al: "Cell-cycle-dependent expression of the STK-1 gene encoding a novel murine putative protein kinase." Gene. 169. 197-201 (1996)
[文献書誌] Igakura,T.,et al: "Roles of basigin,a member of the immunoglobulin superfamily,in behavior as to an irritaing odor,lymphocyte response,and blood-brain barrier." Biochem Biophys Res Commun. 224. 33-36 (1996)
[文献書誌] Araki,M.,et al: "E-selectin binding promotes neutrophil activation in vivo:a study of blood leukocytes in E-selectin transgenic mice." Biochem Biophys Res Commun. 224. 825-830 (1996)
[文献書誌] Okamoto.T.,et al: "TNF-α gene expression in the liver of the IFN-γ transgenic mouse with chronic active hepatitis." Biochem Biophys Res Commun. 226. 762-768 (1996)
[文献書誌] Yoshida,H.,et al: "Neural and skin cell-specific expression pattern conferred by Steel factor regulatory sequence in transgenic mice." Dev Dynamics. 207. 222-232 (1996)
[文献書誌] Abe,K.,et al: "Endoderm-specific gene expression in embryonic stem cells differntiated to embryoid bodies." Exp Cell Res. 229. 27-34 (1996)

1996 年度 実績報告書

標的遺伝子組換えによる生体機能の研究

研究代表者

勝木 元也 東京大学, 医科学研究所, 教授 (20051732)

研究成果

[文献書誌] Suda,Y.,et al.: "Otx1 function overlaps with Otx2 in development of mouse forebrain and midbrain." Genes to Cells. (in press)

[文献書誌] Nakayama,T.,et al: "Fracture healing is a process independent of p53 function." Biochem Biophys Res Commun. (in press)

[文献書誌] Yasunaga,M.,et al: "Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor." J Cell Biol. 132. 1-9 (1996)

[文献書誌] Ilic,D.,et al: "Impairment of mobility in endodermal cells by FAK-deficiency." Exp Cell Res. 222. 298-303 (1996)

[文献書誌] Kanazawa,S.,et al: "Cooperation of p59 fyn and p125FAK in Development of CD4+CD8+Thymocytes." Blood. 87. 865-870 (1996)

[文献書誌] Nanazawa,S.,et al: "Impaired development of CD4+CD8+thymocytes by csk-“knoch-in"into fyn locus." Oncogene. 13. 199-204 (1996)

[文献書誌] Kato,M.V.,et al: "A follistatin-like gene,mac 25,may act as a growth suppressor of osteosarcama cells." Oncogene. 12. 1361-1364 (1996)

[文献書誌] Ishizaki,K.,et al: "UV-induced mutatiioons of supF gene on a shuttle vector plasmid in p53-deficentmouse cells are qualitatively defferent from those in wild-type cells." Mut Res. 364. 43-49 (1996)

[文献書誌] Enokido,Y.,et al: "p-53 involves cytosine arabinoside-induced apoptosis in cultured cerebellar granule neurons" Neurosci Left. 203. 1-4 (1996)

[文献書誌] Yamauchi.T.,et al: "Insulin signalling and actions in the muscles and livers of insulin-resistant,insulin receptor substrate 1-deficient mice." Mol Cellr Biol. 16. 3074-3084 (1996)

[文献書誌] Vuori,K.,et al: "Induction of p130^<cas> signaling complex formation upon integrin-mediated cell adhesion:a role for src family kinase." Mol Cellr Biol. 16. 2606-2613 (1996)

[文献書誌] Enokido,Y.,et al: "Involvement of p53 in DNA stand break-induced apoptosis in postmitotic CNS neurons." Eur J Neurosci. 8. 1812-1821 (1996)

[文献書誌] Shimoji,M.,et al: "Application of primary hepatocytes from p53-knockout mice for studies of expression of Cyp3a" J.Biochem. 120. 42-48 (1996)

[文献書誌] Hamaguchi,I.,et al: "Analysis of CSK homologous kinase(CHK/HYL)in hematopoiesis by utilizing gene knockout mice." Biochem Biophys Res Commun. 224. 172-179 (1996)

[文献書誌] Tanaka,N.,et al: "Cooperation of the tumour suppressors IRF-1 and p53 in response to DNA damage." Nature. 382. 816-818 (1996)

[文献書誌] Hamasaki,K.,et al: "Src kinase plays an essential role in integrin-mediated tyrosine phosphorylation of Crk-associated substrate p130^<Cas>." Biochem Biophys Res Commun. 222. 338-343 (1996)

[文献書誌] Kutsuwada,T.,et al: "Impairment of suckling response,trigeminal neuronal pattern formation and hippocampal LTD in NMDA receptor ε2 subunit mutant mice." Neuron. 16. 333-344 (1996)

[文献書誌] Yoshida,M.,et al: "Emx1 and Emxd2 functions in development of dorsal telencephalon." Development. 122. 4-9 (1996)

[文献書誌] Takamiya,K.,et al: "Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous sustem." Proc Natl Acad Sci USA. 93. 10662-10667 (1996)

[文献書誌] Araki,K.,et al: "Meiotic abnoralities of c-mos knockout mouse oocytes:Activation after first meiosis or entrance into third meiotic metaphase." Biol Rep. 55. 1315-1324 (1996)

[文献書誌] 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)

[文献書誌] Yokoi,M.,et al: "Impariment of hippocampal mossy fiber LTD in mice lacking mGluR2." Scienc. 273. 645-647 (1996)

[文献書誌] Kato,T.,et al: "Inactivation of hepatitis C virus cDNA transgene by hypermethylation intransgenic mice." Arch Virol. 141. 951-958 (1996)

[文献書誌] Inoue,R.,et al: "Rare activation of the human c-Ha-rastransgene of mice in hemangioendothelial sarcomas and liver tumors induced by Glu-P-1." Jpn J Cancer Res. 87. 583-588 (1996)

[文献書誌] 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)

[文献書誌] Li,Y.,et al: "Establishiment of transgenic mice carrying human fetus-specific CYP3A7." Arch Biochem Biophys. 329. 235-240 (1996)

[文献書誌] Gondo,Y.,et al: "A novel positive detection system of in vivo mutations in rpsL(strA)transgenic mice." Mutation Res. 360. 1-14 (1996)

[文献書誌] Norimura,T.,et al: "p53-dependent apoptosis suppresses radeation-induced teratogenesis." Nature Medicine. 2. 577-580 (1996)

[文献書誌] 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)

[文献書誌] Tokita,Y.,et al: "Characterization of excitatory amino acid neurotoxcity in N-methy1-D-aspartate receptor-deficient mouse cortical neuronal cells." Eur J Neurosci. 8. 69-78 (1996)

[文献書誌] Kitamoto.T.,et al: "Humanized prion protein knock-in by Cer-induced site-specific recombination in the mouse." Biochem Biopys Res Commun. 222. 742-747 (1996)

[文献書誌] Tsuzuki,T.,et al: "Targeted disruption of the DNA repair methyltransferase gene renders mice hypersensitive to alkylating agent." Carcinogenesis. 17. 1215-1220 (1996)

[文献書誌] Shibata,H.,et al: "Inactive allele-specific methylation and chromatin structure of the imprinted gene U2afbp-rs1 on mouse Chromosome 11." Genomics. 35. 248-252 (1996)

[文献書誌] Higashi,Y.,et al: "Impairment of T cell development in δEF1 mutant mice." J Exp Med. (in press)

[文献書誌] Shimono,A.,et al: "Requirement of N-myc protein down-regulation for neuronal differentiation in the spinal cord." Dev Growth Differ. 38. 707-717 (1996)

[文献書誌] Sekido,R.,et at: "Organization of the gene encoding transcriptional repressor δEF1 and cross-species conservation of encoded protein domains." Gene. 173. 227-232 (1996)

[文献書誌] Shoji,H.,et al: "Regionalized expression of the Dbx family homeobox genes in the embryonic CNS of the mouse." Mech Dev. 56. 25-39 (1996)

[文献書誌] Watanabe,M.,et al: "Gene transfection of mouse primordial germ cells in vitro and analysis of their survival and growth control." Exp Cell Res. (in press).

[文献書誌] Kawase,E.,et al: "A combination of Buffalo rat liver cell-conditioned medium,forskolin and membrane-bound stem cell factor stimulates rapid proliferation of mouse primordial germ cells in vitro similar to that in vivo." Devel Growth Differ. 38. 315-322 (1996)

[文献書誌] Koshimizu,U.,et al: "Functional requirement of gp130-mediated signaling for growth and survival of mouse primordial germ cells in vitro and derivation of embryonic germ(EG)cells." Dev. 122. 1235-1242 (1996)

[文献書誌] Ohkubo,Y.,et al: "Autonomous regulation of proliferation and growth arrest in mouse primordial germ cells studied by mixed and clonal cultures." Exp Cell Res. 222. 291-297 (1996)

[文献書誌] Nishi,M.,et al: "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking nociceptin/orphaninFQ receptor." EMBOJ. (in press)

[文献書誌] Matsumoto,M.,et al: "Ataxia and epileptic seizure in mice lacking type 1 inositol 1,4,5-trisphophate receptor." Nature. 379. 168-171 (1996)

[文献書誌] Sakaguchi,S.,et al: "Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene." Nature. 380. 528-531 (1996)

[文献書誌] Takeshima,H.,et al: "Generation and characterization of mutant mice lacking ryanodine receptor type3." J Biol Chem. 271. 19649 (1996)

[文献書誌] Nagata,A.,et al: "G protein-coupled cholecystokinin-B/gastrin receptors are responsible for physiological cell growth of the stomach mucosa in vivo." Proc Natl Acad Sci USA. 93. 11825-11830 (1996)

[文献書誌] Shimada,A.,et al: "Immune response to heat-shock protein correlates with induction of insulitis in I-Eαd transgenic NOD mice" Diabetes. 45. 165-169 (1996)

[文献書誌] Kaname,T.,et al: "The expression of trunccated MKin human tumors." Biochem Biophys Res Commun. 219. 256-260 (1996)

[文献書誌] Niwa,H.,et al: "Cell-cycle-dependent expression of the STK-1 gene encoding a novel murine putative protein kinase." Gene. 169. 197-201 (1996)

[文献書誌] Igakura,T.,et al: "Roles of basigin,a member of the immunoglobulin superfamily,in behavior as to an irritaing odor,lymphocyte response,and blood-brain barrier." Biochem Biophys Res Commun. 224. 33-36 (1996)

[文献書誌] Araki,M.,et al: "E-selectin binding promotes neutrophil activation in vivo:a study of blood leukocytes in E-selectin transgenic mice." Biochem Biophys Res Commun. 224. 825-830 (1996)

[文献書誌] Okamoto.T.,et al: "TNF-α gene expression in the liver of the IFN-γ transgenic mouse with chronic active hepatitis." Biochem Biophys Res Commun. 226. 762-768 (1996)

[文献書誌] Yoshida,H.,et al: "Neural and skin cell-specific expression pattern conferred by Steel factor regulatory sequence in transgenic mice." Dev Dynamics. 207. 222-232 (1996)

[文献書誌] Abe,K.,et al: "Endoderm-specific gene expression in embryonic stem cells differntiated to embryoid bodies." Exp Cell Res. 229. 27-34 (1996)

1996 年度実績報告書

勝木元也東京大学, 医科学研究所, 教授 (20051732)