1994 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	九州大学
研究代表者	勝木元也九州大学, 生体防御医学研究所, 教授 (20051732)
研究分担者	関口睦夫九州大学, 生体防御医学研究所, 教授 (00037342) 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, 教授 (60073011) 山村研一熊本大学, 医学部, 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 / myogenin / tau
研究概要	本研究は標的遺伝子組換え法を用いて、標的とする遺伝子に突然変異を導入し、それに伴う生体の形質の変化を通して、現代のバイオサイエンスの大きな課題の一つである固体レベルでの遺伝子機能を研究することを目的とする。総括班である本班は、計画研究班と公募研究班員の研究とを評価し、成果が目標に向かっているかを検討し、班員相互の協力体制を励まし、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。また、本研究は、その方法論に大きな特徴と実現の困難さとがあることから、本邦において将来においては専門的に実施する施設を数カ所に設定する必要性が論じられた。そこで、総括班から重点配分として、九大、および熊大、に配分され、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、グルタミン酸受容体(NMDAタイプ5種、メタボトロピックタイプ6種)セロトニン受容体、ドーパミン受容体、P53、H-ras、N-ras、K-ras、tau、GFAP、免疫グロブリン遺伝子、APC、myogeninなどすでに20種を越えている。これらのマウスを作成する力が、日本中にこの一年間でさらに大きく広がったものと確信される。

研究成果

(32件)

すべてその他

すべて文献書誌 (32件)

[文献書誌] 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)
[文献書誌] Sato,M.,et al.: "Naive T cells can mediate delayed-type hypersensitivity response in T cell receptor transgenic mice." Eur J Immunol. 24. 1512-1516 (1994)
[文献書誌] Lafaille,JJ.,et al.: "High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein Tcell receptor transgenic mice." Cell. 78. 399-408 (1994)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Nishiyori,A.,et al.: "Determination of tissue specificity of the enhancer by combinatorial operation of tissue-enriched transcription factors." J Biol Chem. 269. 1323-1331 (1994)
[文献書誌] Toyonaga,T.,et al.: "Chronic active hepatitis in transgenic mice expressing interferon-γ in the liver." Proc Natl Acad Sci USA. 91. 614-618 (1994)
[文献書誌] Kaname,T.,et al.: "The upstream sequence of a new growth/diffrentiation factor,midkine(MK),mediates developmentally regulated lacZ gene expression in transgenic mice." Dev Growth Differ. 36. 231-238 (1994)
[文献書誌] Yamashita,S.,et al.: "Group II phospholipase A2 in invasive gastric cancer cell line is induced by interleukin 6." Biochem Biophys Res Commun. 198. 878-884 (1994)
[文献書誌] Nishiyama,T.,et al.: "Expression of the gene encoding the tyrosine kinase-deficient human insulin receptor in transgenic mice." Gene. 141. 187-192 (1994)
[文献書誌] Imamura,F.,et al.: "The murine interleukin-5 receptor a-subunit gene:charcterization of the gene structure and chromosome mapping." DNA Cell Biol. 13. 283-292 (1994)
[文献書誌] Araki,S.,et al.: "Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin (Met30) gene." Mol Neurobiol. 8. 15-23 (1994)
[文献書誌] Tashiro,F.,et al.: "Resistance to cyclophosphamide-induced diabetes in transgenic NOD mice expressing I-A^k." Autoimmunity. 17. 181-188 (1994)
[文献書誌] Mantani,A.,et al.: "A novel isoform of the neurofibromatosis type-1 mRNA and a switch of isoforms during murine cell differentiation and proliferation." Gene. 148. 254-251 (1994)
[文献書誌] Kimura,S.,et al.: "Improvement of germ line transmission by targeting β-galactosidase to nuclei in transgenic mice." Dev Growth Differ. 36. 521-527 (1994)
[文献書誌] Nada,S.,et al.: "Identification of major tyrosine-phosphorylatedproteins in Csk-deficient cells." Oncogene. 9. 3571-3578 (1994)
[文献書誌] Umemori,H.,et al.: "Initial events of myelination involve Fyn tyrosine kinase signalling." Nature. 367. 572-576 (1994)
[文献書誌] Kubo,S.,et al.: "A novel form of self tolerance dictated in the thymus of transgenic mice with autoreactive TCRα and β chain genes." Int Immunol. 6. 593-602 (1994)
[文献書誌] 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)
[文献書誌] Yagi,T.,et al.: "Fyn expression during neurogenesis in mouse embryos." Oncogene. 9. 2433-2440 (1994)
[文献書誌] Tanaka,N.,et al.: "Cellular commitment to oncogene-induced transformation or apoptosisis dependent on the transcription factor IRF-1." Cell. 77. 829-839 (1994)
[文献書誌] Kohmura,N.,et al.: "A novel non-receptor tyrosine kinase,srm;cloning and targeted disruption." Mol Cell Biol. 14. 6915-6925 (1994)
[文献書誌] Ishizaki,K.,et al.: "Increased UV-induced SCEs in p53-deficient mouse cells." INt J Cancer. 58. 254-257 (1994)
[文献書誌] 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)
[文献書誌] Sekido,R.,et al.: "The δ-crystallin enhancer-binding protein δEF1 is a repressor of E2-box-mediated gene activation." Mol Cell Biol. 14. 5692-5700 (1994)
[文献書誌] Takahashi,Y.,et al.: "Lens-specific activity of the chicken d1-crystallin enhancer in the mouse." Int J.Dev.Biol. 38. 365-368 (1994)
[文献書誌] Kawaase,E.,et al.: "Strain difference in establishment of mouse embryonic stem (ES) cell lines." Int J Dev Biol. 38. 385-390 (1994)
[文献書誌] Kawase,E.,et al.: "Tumor necrosis factor-α(TNF-α) stimulates proliferation of mouse primordial germ cells in culture." Dev Biol. 161. 95 (1994)
[文献書誌] Furuichi,M.,et al.: "Genomic structure and chromosome location of the human mutT homolog gene hMTH1 encoding 8-oxo-dGTPase for prevention of A.T to C:Gtransversion." Genomics. 24. 485-490 (1994)
[文献書誌] 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)
[文献書誌] 勝木元也: "血小板の分子生物学" 金芳堂, 190 (1994)

1994 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 九州大学, 生体防御医学研究所, 教授 (20051732)

研究成果

[文献書誌] 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)

[文献書誌] Sato,M.,et al.: "Naive T cells can mediate delayed-type hypersensitivity response in T cell receptor transgenic mice." Eur J Immunol. 24. 1512-1516 (1994)

[文献書誌] Lafaille,JJ.,et al.: "High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein Tcell receptor transgenic mice." Cell. 78. 399-408 (1994)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] Nishiyori,A.,et al.: "Determination of tissue specificity of the enhancer by combinatorial operation of tissue-enriched transcription factors." J Biol Chem. 269. 1323-1331 (1994)

[文献書誌] Toyonaga,T.,et al.: "Chronic active hepatitis in transgenic mice expressing interferon-γ in the liver." Proc Natl Acad Sci USA. 91. 614-618 (1994)

[文献書誌] Kaname,T.,et al.: "The upstream sequence of a new growth/diffrentiation factor,midkine(MK),mediates developmentally regulated lacZ gene expression in transgenic mice." Dev Growth Differ. 36. 231-238 (1994)

[文献書誌] Yamashita,S.,et al.: "Group II phospholipase A2 in invasive gastric cancer cell line is induced by interleukin 6." Biochem Biophys Res Commun. 198. 878-884 (1994)

[文献書誌] Nishiyama,T.,et al.: "Expression of the gene encoding the tyrosine kinase-deficient human insulin receptor in transgenic mice." Gene. 141. 187-192 (1994)

[文献書誌] Imamura,F.,et al.: "The murine interleukin-5 receptor a-subunit gene:charcterization of the gene structure and chromosome mapping." DNA Cell Biol. 13. 283-292 (1994)

[文献書誌] Araki,S.,et al.: "Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin (Met30) gene." Mol Neurobiol. 8. 15-23 (1994)

[文献書誌] Tashiro,F.,et al.: "Resistance to cyclophosphamide-induced diabetes in transgenic NOD mice expressing I-A^k." Autoimmunity. 17. 181-188 (1994)

[文献書誌] Mantani,A.,et al.: "A novel isoform of the neurofibromatosis type-1 mRNA and a switch of isoforms during murine cell differentiation and proliferation." Gene. 148. 254-251 (1994)

[文献書誌] Kimura,S.,et al.: "Improvement of germ line transmission by targeting β-galactosidase to nuclei in transgenic mice." Dev Growth Differ. 36. 521-527 (1994)

[文献書誌] Nada,S.,et al.: "Identification of major tyrosine-phosphorylatedproteins in Csk-deficient cells." Oncogene. 9. 3571-3578 (1994)

[文献書誌] Umemori,H.,et al.: "Initial events of myelination involve Fyn tyrosine kinase signalling." Nature. 367. 572-576 (1994)

[文献書誌] Kubo,S.,et al.: "A novel form of self tolerance dictated in the thymus of transgenic mice with autoreactive TCRα and β chain genes." Int Immunol. 6. 593-602 (1994)

[文献書誌] 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)

[文献書誌] Yagi,T.,et al.: "Fyn expression during neurogenesis in mouse embryos." Oncogene. 9. 2433-2440 (1994)

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

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

[文献書誌] Ishizaki,K.,et al.: "Increased UV-induced SCEs in p53-deficient mouse cells." INt J Cancer. 58. 254-257 (1994)

[文献書誌] 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)

[文献書誌] Sekido,R.,et al.: "The δ-crystallin enhancer-binding protein δEF1 is a repressor of E2-box-mediated gene activation." Mol Cell Biol. 14. 5692-5700 (1994)

[文献書誌] Takahashi,Y.,et al.: "Lens-specific activity of the chicken d1-crystallin enhancer in the mouse." Int J.Dev.Biol. 38. 365-368 (1994)

[文献書誌] Kawaase,E.,et al.: "Strain difference in establishment of mouse embryonic stem (ES) cell lines." Int J Dev Biol. 38. 385-390 (1994)

[文献書誌] Kawase,E.,et al.: "Tumor necrosis factor-α(TNF-α) stimulates proliferation of mouse primordial germ cells in culture." Dev Biol. 161. 95 (1994)

[文献書誌] Furuichi,M.,et al.: "Genomic structure and chromosome location of the human mutT homolog gene hMTH1 encoding 8-oxo-dGTPase for prevention of A.T to C:Gtransversion." Genomics. 24. 485-490 (1994)

[文献書誌] 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)

[文献書誌] 勝木元也: "血小板の分子生物学" 金芳堂, 190 (1994)

1994 年度実績報告書

勝木元也九州大学, 生体防御医学研究所, 教授 (20051732)