1997 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, 細胞生物, 部長 (10183550) 中辻憲夫国立遺伝学研究所, 遺伝実験生物保存研究センター, 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	標的遺伝子組替え / ジーンターゲッテイング / 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	本実績報告書は、平成5年度〜8年度文部省科学研究費補助金(重点領域研究)「標的遺伝子組換えによる生体機能の研究」の研究成果をとりまとめたものである。本領域研究では、2つの計画研究の班員と公募研究の班員とが個体の遺伝子操作法の確立と普及、研究への自在な応用、そして、それから得られる生体機能の分子生物学的理解を目的とした。この目的を達成するために、個体レベルでの生体機能を、遺伝子工学、ES細胞工学、発生工学の3分野の知識と技術とを、複合的に組み合わせた標的遺伝子組換え法を用いて進めてきた。その結果、ノックアウトされた遺伝子は本研究班員だけで、約300にのぼり、そのうちの多くが発表され、また報告準備中である。本研究によって得られた成果を列挙すれば、p53、H-ras、N-ras、K-ras、APCなどのがん遺伝子、ドーパミン受容体、グルタミン酸受容体、セロトニン受容体などの脳機能に関与する遺伝子をはじめ形態形成に関与する転写因子など、多くの分子生物学的解析に貢献した。

研究成果
(39件)

すべてその他

すべて文献書誌 (39件)

[文献書誌] Koera,K., et al.: "K-Ras is essential for the development of the mouse embryo." Oncogene. 15. 1151-1159 (1997)
[文献書誌] Mimura,J., et al.: "Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)in mice lacking the Ah(dioxin)receptor." Gene to Cells. 2. 645-654 (1997)
[文献書誌] Araki,E., et al.: "Targeted disruption of exon 52 in the mouse dystrophin gene induced muscle degeneration similar to that observed in Duchenne muscular dystrophy." Biochem Biophys Res Commun. 238. 492-497 (1997)
[文献書誌] Nakao,K., et al.: "Simple and efficient vitrification procedure for cryopreservation of mouse embryos." Exp Anim. 46. 231-234 (1997)
[文献書誌] Fukui,Y., et al.: "Positive and negative CD4+thymocyte selection by a single MHC class II/peptide ligand affected by its expression level in the thymus." Immunity. 6. 401-410 (1997)
[文献書誌] Ohmi,K., et al.: "A novel aortic smooth muscle cell line obtained from p53 knock out mice expresses several differentiation characteristics." Biochem Biophys Res Commun. 238. 154-158 (1997)
[文献書誌] Kameya,S., et al.: "Dp260 disrupted mice revealed prolonged implicit time of the b-wave in ERG and loss of accumulation of b-dystroglycan in the outer plexiform layer of the retina." Hum Mol Genet. 6. 2195-2203 (1997)
[文献書誌] Shibata,H., et al.: "An oocyte-specific methylation imprint center in the mouse U2afbp-rs/U2afl-rsl gene marks the establishment of allele-specific methylation during preimplantation development." Genomics. 44. 171-178 (1997)
[文献書誌] Araki,K., et al.: "Targeted integration of DNA using mutant lox sites in embryonic stem cells." Nucleic Acid Res. 25. 868-872 (1997)
[文献書誌] Kimura,S., et al.: "2.1 kb 5'-flanking region of the brain type dystrophin gene directs the expression of lacZ in the cerebral cortex,but not in the hippocampus." J Neurol Sci. 147. 13-20 (1997)
[文献書誌] Kohno,K., et al.: "Analysis of amyloid deposition in a transgenic mouse model of homozygous familial amyloidotic polyneuropathy." Amer J Pathol. 150. 1497-1508 (1997)
[文献書誌] Kimura.S., et al.: "A 900bp genomic region from the mouse dystrophin promoter directs lacZ reporter expression only to the right heart of transgenic mice." Dev Growth Differ. 39. 257-265 (1997)
[文献書誌] Tanahashi,N., et al.: "Molecular properties of the proteasome activator PA28 family proteins and γ-interferon regulation." Genes Cells. 2. 195-211 (1997)
[文献書誌] Suda,Y., et al.: "Cooperation between Otx1 and Otx2 genes in developemtal patterning of rostral brain." Mechanisms of Development. 69. 1-17 (1997)
[文献書誌] Nitta,M., et al.: "Heat shock induces trancient p53-dependent cell cycle arrest at G1/S." Oncogene. 15. 561-568 (1997)
[文献書誌] Kimura,C., et al.: "Cis-acting elements conserved between mouse and pufferfish Otx2 genes govern the expression in mesencephalic neural crest cells." Dev Suppl. 124. 3929-3941 (1997)
[文献書誌] Nakamoto,T., et al.: "Requirements for localization of p130cas to focal adhesions." Mol Cell Biol. 17. 3884-3897 (1997)
[文献書誌] Ilic,D., et al.: "Skin abnormality in aged fyn-/-fak+/-mice." Carcinogenesis. 18. 1473-1476 (1997)
[文献書誌] Sakai,R., et al.: "Characterization of the kinase activity essentiol for tyrosine phosphorylation of p130cas in fibroblasts." Oncogene. 14. 1419-1426 (1997)
[文献書誌] Kano,A., et al.: "Analysis of IFN-γ induced cell cycle arrest and cell death in hepatocytes." J Biochem. 121. 677-683 (1997)
[文献書誌] Miyamoto,N., et al.: "Defects of urogenital development in mice lacking Emx2." Development. 124. 1653-1664 (1997)
[文献書誌] Oda,H., et al.: "Loss of p53 is an early event in induction of brain tumors in mice by transplacental carcinogen exposure." Cancer Res. 57. 646-650 (1997)
[文献書誌] Kuratani,S., et al.: "Developmental patterning and evolution of the mammalian viscerocranium genetic insights into comparative morphology." Dev Dyn. 209. 139-155 (1997)
[文献書誌] Kuratani,S., et al.: "Peripheral development of cranial nerves in a cyclostome,Lampetra japonica Morphological destribution of nerve branches and the vertebrate body plan." J Comparative Neurol. 384. 483-500 (1997)
[文献書誌] Yoshida,M., et al.: "Emx1 and Emx2 functions in development of dorsal telencephalon." Development. 124. 101-111 (1997)
[文献書誌] Sasaki,H., et al.: "A binding site for Gli protein is essential for HNF-3b floor plate enhancer activity and is a Shh responsive element." Development. 124. 1313-1322 (1997)
[文献書誌] Wakamatsu,Y., et al.: "Regulation of the neural crest cell fate by N-myc:promotion of ventral migration and neuronal differentiation." Development. 124. 1953-1962 (1997)
[文献書誌] Higashi,Y., et al.: "Impairment of T cell development in δEF1 mutant mice." J Exp Med. 185. 1467-1479 (1997)
[文献書誌] Shirayoshi,Y., et al.: "Proto-oncogene int-3,a mouse Notch homologue,is expressed in endothelial cells during early embryogenesis." Genes Cells. 2. 213-224 (1997)
[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. 230. 76-83 (1997)
[文献書誌] Shibata,H., et al.: "Rapid colorectal adenoma formation initiated by conditional targeting of the APC gene." Science. 278. 120-123 (1997)
[文献書誌] Shiba,K., et al.: "Human lysyl-tRNA synthetase accepts N73 variants and rescues escherichia double-defective mutant." J Biol Chem. 272. 22809-22816 (1997)
[文献書誌] Takei,Y., et al.: "Delayed development of nervous system in mice homozygous for disrupted microtubule-associated protein 1B(MAP1B)gene." J Cell Biol. 137. 1615-1626 (1997)
[文献書誌] Wakabayashi,Y., et al.: "Genetic and physical delineation of the region of the mouse deafness mouse deafness mutation shaker-2." Biochem Biophys Res Commun. 232. 107-110 (1997)
[文献書誌] Terunuma,A., et al.: "A novel genetic system to isolate a domonant negative effecter on DNA-binding activity of Oct-2." Nucleic Acid Res. 25. 1984-1990 (1997)
[文献書誌] Niki,M., et al.: "Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor,PEBP2/CBP." Proc Natl Acad Sci USA. 94. 5697-5702 (1997)
[文献書誌] Shiba,K., et al.: "Creation of libraries with long openreading frames by polymerization of a microgene." Proc Natl Acad Sci USA. 94. 3805-3810 (1997)
[文献書誌] Suzuki,H., et al.: "A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection." Nature. 386. 292-296 (1997)
[文献書誌] Nishi,M., et al.: "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking nociceptin/orphaninFQ receptor." EMBOJ. 16. 1858-1864 (1997)

1997 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] Koera,K., et al.: "K-Ras is essential for the development of the mouse embryo." Oncogene. 15. 1151-1159 (1997)

[文献書誌] Mimura,J., et al.: "Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)in mice lacking the Ah(dioxin)receptor." Gene to Cells. 2. 645-654 (1997)

[文献書誌] Araki,E., et al.: "Targeted disruption of exon 52 in the mouse dystrophin gene induced muscle degeneration similar to that observed in Duchenne muscular dystrophy." Biochem Biophys Res Commun. 238. 492-497 (1997)

[文献書誌] Nakao,K., et al.: "Simple and efficient vitrification procedure for cryopreservation of mouse embryos." Exp Anim. 46. 231-234 (1997)

[文献書誌] Fukui,Y., et al.: "Positive and negative CD4+thymocyte selection by a single MHC class II/peptide ligand affected by its expression level in the thymus." Immunity. 6. 401-410 (1997)

[文献書誌] Ohmi,K., et al.: "A novel aortic smooth muscle cell line obtained from p53 knock out mice expresses several differentiation characteristics." Biochem Biophys Res Commun. 238. 154-158 (1997)

[文献書誌] Kameya,S., et al.: "Dp260 disrupted mice revealed prolonged implicit time of the b-wave in ERG and loss of accumulation of b-dystroglycan in the outer plexiform layer of the retina." Hum Mol Genet. 6. 2195-2203 (1997)

[文献書誌] Shibata,H., et al.: "An oocyte-specific methylation imprint center in the mouse U2afbp-rs/U2afl-rsl gene marks the establishment of allele-specific methylation during preimplantation development." Genomics. 44. 171-178 (1997)

[文献書誌] Araki,K., et al.: "Targeted integration of DNA using mutant lox sites in embryonic stem cells." Nucleic Acid Res. 25. 868-872 (1997)

[文献書誌] Kimura,S., et al.: "2.1 kb 5'-flanking region of the brain type dystrophin gene directs the expression of lacZ in the cerebral cortex,but not in the hippocampus." J Neurol Sci. 147. 13-20 (1997)

[文献書誌] Kohno,K., et al.: "Analysis of amyloid deposition in a transgenic mouse model of homozygous familial amyloidotic polyneuropathy." Amer J Pathol. 150. 1497-1508 (1997)

[文献書誌] Kimura.S., et al.: "A 900bp genomic region from the mouse dystrophin promoter directs lacZ reporter expression only to the right heart of transgenic mice." Dev Growth Differ. 39. 257-265 (1997)

[文献書誌] Tanahashi,N., et al.: "Molecular properties of the proteasome activator PA28 family proteins and γ-interferon regulation." Genes Cells. 2. 195-211 (1997)

[文献書誌] Suda,Y., et al.: "Cooperation between Otx1 and Otx2 genes in developemtal patterning of rostral brain." Mechanisms of Development. 69. 1-17 (1997)

[文献書誌] Nitta,M., et al.: "Heat shock induces trancient p53-dependent cell cycle arrest at G1/S." Oncogene. 15. 561-568 (1997)

[文献書誌] Kimura,C., et al.: "Cis-acting elements conserved between mouse and pufferfish Otx2 genes govern the expression in mesencephalic neural crest cells." Dev Suppl. 124. 3929-3941 (1997)

[文献書誌] Nakamoto,T., et al.: "Requirements for localization of p130cas to focal adhesions." Mol Cell Biol. 17. 3884-3897 (1997)

[文献書誌] Ilic,D., et al.: "Skin abnormality in aged fyn-/-fak+/-mice." Carcinogenesis. 18. 1473-1476 (1997)

[文献書誌] Sakai,R., et al.: "Characterization of the kinase activity essentiol for tyrosine phosphorylation of p130cas in fibroblasts." Oncogene. 14. 1419-1426 (1997)

[文献書誌] Kano,A., et al.: "Analysis of IFN-γ induced cell cycle arrest and cell death in hepatocytes." J Biochem. 121. 677-683 (1997)

[文献書誌] Miyamoto,N., et al.: "Defects of urogenital development in mice lacking Emx2." Development. 124. 1653-1664 (1997)

[文献書誌] Oda,H., et al.: "Loss of p53 is an early event in induction of brain tumors in mice by transplacental carcinogen exposure." Cancer Res. 57. 646-650 (1997)

[文献書誌] Kuratani,S., et al.: "Developmental patterning and evolution of the mammalian viscerocranium genetic insights into comparative morphology." Dev Dyn. 209. 139-155 (1997)

[文献書誌] Kuratani,S., et al.: "Peripheral development of cranial nerves in a cyclostome,Lampetra japonica Morphological destribution of nerve branches and the vertebrate body plan." J Comparative Neurol. 384. 483-500 (1997)

[文献書誌] Yoshida,M., et al.: "Emx1 and Emx2 functions in development of dorsal telencephalon." Development. 124. 101-111 (1997)

[文献書誌] Sasaki,H., et al.: "A binding site for Gli protein is essential for HNF-3b floor plate enhancer activity and is a Shh responsive element." Development. 124. 1313-1322 (1997)

[文献書誌] Wakamatsu,Y., et al.: "Regulation of the neural crest cell fate by N-myc:promotion of ventral migration and neuronal differentiation." Development. 124. 1953-1962 (1997)

[文献書誌] Higashi,Y., et al.: "Impairment of T cell development in δEF1 mutant mice." J Exp Med. 185. 1467-1479 (1997)

[文献書誌] Shirayoshi,Y., et al.: "Proto-oncogene int-3,a mouse Notch homologue,is expressed in endothelial cells during early embryogenesis." Genes Cells. 2. 213-224 (1997)

[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. 230. 76-83 (1997)

[文献書誌] Shibata,H., et al.: "Rapid colorectal adenoma formation initiated by conditional targeting of the APC gene." Science. 278. 120-123 (1997)

[文献書誌] Shiba,K., et al.: "Human lysyl-tRNA synthetase accepts N73 variants and rescues escherichia double-defective mutant." J Biol Chem. 272. 22809-22816 (1997)

[文献書誌] Takei,Y., et al.: "Delayed development of nervous system in mice homozygous for disrupted microtubule-associated protein 1B(MAP1B)gene." J Cell Biol. 137. 1615-1626 (1997)

[文献書誌] Wakabayashi,Y., et al.: "Genetic and physical delineation of the region of the mouse deafness mouse deafness mutation shaker-2." Biochem Biophys Res Commun. 232. 107-110 (1997)

[文献書誌] Terunuma,A., et al.: "A novel genetic system to isolate a domonant negative effecter on DNA-binding activity of Oct-2." Nucleic Acid Res. 25. 1984-1990 (1997)

[文献書誌] Niki,M., et al.: "Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor,PEBP2/CBP." Proc Natl Acad Sci USA. 94. 5697-5702 (1997)

[文献書誌] Shiba,K., et al.: "Creation of libraries with long openreading frames by polymerization of a microgene." Proc Natl Acad Sci USA. 94. 3805-3810 (1997)

[文献書誌] Suzuki,H., et al.: "A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection." Nature. 386. 292-296 (1997)

[文献書誌] Nishi,M., et al.: "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking nociceptin/orphaninFQ receptor." EMBOJ. 16. 1858-1864 (1997)

1997 年度実績報告書

勝木元也東京大学, 医科学研究所, 教授 (20051732)