1995 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	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 / 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を研究することを目的とする。本班は、2つの計画研究班と公募研究とからなり、班員の研究を評価し、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、マウスなどの動物個体を用いることから、技術はもちろん、施設、費用の点で実現に困難さがあり、どこでも、いつでも、実施可能でないところが問題である。そこで本邦では将来においては専門的実施施設を数カ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、九大、東大、および熊大、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90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

(33件)

すべてその他

すべて文献書誌 (33件)

[文献書誌] Kashiwabuchi,N.,et al.: "Impairment of motor coordination, Purkinje cell synapse formation and cerebellar long-term depression in GluRδ2 mutant mice." Cell. 81. 245-252 (1995)
[文献書誌] Ilic,D.,et al.: "Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice." Nature. 377. 539-544 (1995)
[文献書誌] Tamura,T.,et al.: "An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes." Nature. 376. 596-599 (1995)
[文献書誌] Sakimura,K.,et al.: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit." Nature. 373. 151-155 (1995)
[文献書誌] Ikeda,K.,et al.: "Reduced spontaneous activity of mice defective in the ε4 subunit of the NMDA receptor channel." Mol Brain Res. 33. 61-71 (1995)
[文献書誌] Fruta,Y.,et al.: "Ovarian teratomas in mice lacking the protooncogene, c-Mos." Jpn J Cancer Res. 86. 540-545 (1995)
[文献書誌] Furuta,Y.,et al.: "Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK." Oncogene. 11. 1989-1995 (1995)
[文献書誌] Matsuo,I.,et al.: "Mouse Otx2 fiunctions in the formation and patterning of rostral head." Genes Development. 9. 2646-2658 (1995)
[文献書誌] Yamaguchi,H.,et al.: "Dopamine D2 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituitary." Cenes to Cells. (in press).
[文献書誌] Gondo,Y.,et al.: "A novel positive detection system of in vivo mutations in rpsL(strA)transgenic mice." Mutation Res. (in press).
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Honda,H.,et al.: "Increased tyrosine-phosphorylation of 55KDa proteins in beta-actin/Tec transgenic mice." Biochem Biophys Rea Commun. 206. 287-293 (1995)
[文献書誌] Tamura,H.,et al.: "Opaque eyes developed in transgenic mice with T-cell receptor δ gene." Invest Ophthalmol Vis Sci. 36. 467-477 (1995)
[文献書誌] Yoshida,M.,et al.: "A new strategy of gene-trapping in ES cells using 3′RACE." Transgenic Res. 4. 277-287 (1995)
[文献書誌] Hu,L.,et al.: "P53 controls proliferation of early B lineage cells by a p21(WAF1/CIP1)-independent pathway." Biochem Biophys Res Commun. 206. 948-954 (1995)
[文献書誌] Kanazawa,S.,et al.: "Integrin stimulation decreases ryrosine phosphorylation and activity of focal adhesion kinase in thymocytes." Biochem Biophys Res Commun. 215. 438-445 (1995)
[文献書誌] Ilic,D.,et al.: "Focal adhesion kinase is not essential for in vitro and in vivo differentiation of ES cells." Biochem Biophys Res Commun. 209. 300-309 (1995)
[文献書誌] Tobe,K.,et al.: "Identification of a 190-kDa protein as a novel substrate for the insulin receptor kinase functionally similar to insulin receptor substrate-1." J Biol Chem. 270. 5698-5701 (1995)
[文献書誌] Gross,JA.,et al.: "Control of lymphogenesis by p^<50csk>, a regulatory protein tyrosine kinase." J.Exp Med. 181. 463-473 (1995)
[文献書誌] Kuratani,S.,et al.: "Patterning of the cranial nerves in the chick embryo is dependent on cranial mesoderm and rhombomeric metamerism." Develop Growth Differ. 37. 717-731 (1995)
[文献書誌] Shigetani,Y.,et al.: "Overlapping origins of pharyngeal arch crest cells on the postotic hind-brain." Develop Growth Differ. 37. 733-746 (1995)
[文献書誌] Sekido,R.,et al.: "Organization of the gene encoding transcriptional repressor dEF1 and cross species conservation of encoded protein domains." Gene. (in press.).
[文献書誌] Kamachi,Y.,et al.: "Invovement of SOX proteins in lens-specific activation of crystallin genes." EMBO J. 14. 3510-3519 (1995)
[文献書誌] Kamada,S.,et al.: "Bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated cell death in thymus and spleen, polystic kidney, hair hypopigmentation, and distorted small intestine." Cancer Res. 55. 354-359 (1995)
[文献書誌] Kitsukawa,T.,et al.: "Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limb." Development. 121. 4309-4318 (1995)
[文献書誌] Mikita,R.,et al.: "Transgenesis of newt with exogenous gene expression facilitated by satellite 2 repeats." Dev Growth Differ. 37. 605-616 (1995)
[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(in press.).
[文献書誌] Koshimizu,U.,et al.: "Retinoic acid is a potent growth activator of mouse primordial germ cells in vitro." Devel Biol. 168. 683-685 (1995)
[文献書誌] Nagata,Y.,et al.: "A 6-kb upstream region of the human transthyretin gene van direct developmental tissue-specific, and quantitatively normal expression in transgenic mouse." J Biochem. 117. 169-175 (1995)
[文献書誌] Kitamura,D.,et al.: "Molecular cloning and characterization of mouse HS1." Biochem Biophys Res Commun.208. 1137-1146 (1995)
[文献書誌] Yagui,K.,et al.: "Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin." Eur J Endocrinol. 132. 487-496 (1995)
[文献書誌] Hishido,K.,et al.: "Copy-dependent and position-independent expression of rat aldolase A gene." J Biochem. 118. 601-606 (1995)

1995 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] Kashiwabuchi,N.,et al.: "Impairment of motor coordination, Purkinje cell synapse formation and cerebellar long-term depression in GluRδ2 mutant mice." Cell. 81. 245-252 (1995)

[文献書誌] Ilic,D.,et al.: "Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice." Nature. 377. 539-544 (1995)

[文献書誌] Tamura,T.,et al.: "An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes." Nature. 376. 596-599 (1995)

[文献書誌] Sakimura,K.,et al.: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit." Nature. 373. 151-155 (1995)

[文献書誌] Ikeda,K.,et al.: "Reduced spontaneous activity of mice defective in the ε4 subunit of the NMDA receptor channel." Mol Brain Res. 33. 61-71 (1995)

[文献書誌] Fruta,Y.,et al.: "Ovarian teratomas in mice lacking the protooncogene, c-Mos." Jpn J Cancer Res. 86. 540-545 (1995)

[文献書誌] Furuta,Y.,et al.: "Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK." Oncogene. 11. 1989-1995 (1995)

[文献書誌] Matsuo,I.,et al.: "Mouse Otx2 fiunctions in the formation and patterning of rostral head." Genes Development. 9. 2646-2658 (1995)

[文献書誌] Yamaguchi,H.,et al.: "Dopamine D2 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituitary." Cenes to Cells. (in press).

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

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] Honda,H.,et al.: "Increased tyrosine-phosphorylation of 55KDa proteins in beta-actin/Tec transgenic mice." Biochem Biophys Rea Commun. 206. 287-293 (1995)

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

[文献書誌] Yoshida,M.,et al.: "A new strategy of gene-trapping in ES cells using 3′RACE." Transgenic Res. 4. 277-287 (1995)

[文献書誌] Hu,L.,et al.: "P53 controls proliferation of early B lineage cells by a p21(WAF1/CIP1)-independent pathway." Biochem Biophys Res Commun. 206. 948-954 (1995)

[文献書誌] Kanazawa,S.,et al.: "Integrin stimulation decreases ryrosine phosphorylation and activity of focal adhesion kinase in thymocytes." Biochem Biophys Res Commun. 215. 438-445 (1995)

[文献書誌] Ilic,D.,et al.: "Focal adhesion kinase is not essential for in vitro and in vivo differentiation of ES cells." Biochem Biophys Res Commun. 209. 300-309 (1995)

[文献書誌] Tobe,K.,et al.: "Identification of a 190-kDa protein as a novel substrate for the insulin receptor kinase functionally similar to insulin receptor substrate-1." J Biol Chem. 270. 5698-5701 (1995)

[文献書誌] Gross,JA.,et al.: "Control of lymphogenesis by p^<50csk>, a regulatory protein tyrosine kinase." J.Exp Med. 181. 463-473 (1995)

[文献書誌] Kuratani,S.,et al.: "Patterning of the cranial nerves in the chick embryo is dependent on cranial mesoderm and rhombomeric metamerism." Develop Growth Differ. 37. 717-731 (1995)

[文献書誌] Shigetani,Y.,et al.: "Overlapping origins of pharyngeal arch crest cells on the postotic hind-brain." Develop Growth Differ. 37. 733-746 (1995)

[文献書誌] Sekido,R.,et al.: "Organization of the gene encoding transcriptional repressor dEF1 and cross species conservation of encoded protein domains." Gene. (in press.).

[文献書誌] Kamachi,Y.,et al.: "Invovement of SOX proteins in lens-specific activation of crystallin genes." EMBO J. 14. 3510-3519 (1995)

[文献書誌] Kamada,S.,et al.: "Bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated cell death in thymus and spleen, polystic kidney, hair hypopigmentation, and distorted small intestine." Cancer Res. 55. 354-359 (1995)

[文献書誌] Kitsukawa,T.,et al.: "Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limb." Development. 121. 4309-4318 (1995)

[文献書誌] Mikita,R.,et al.: "Transgenesis of newt with exogenous gene expression facilitated by satellite 2 repeats." Dev Growth Differ. 37. 605-616 (1995)

[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(in press.).

[文献書誌] Koshimizu,U.,et al.: "Retinoic acid is a potent growth activator of mouse primordial germ cells in vitro." Devel Biol. 168. 683-685 (1995)

[文献書誌] Nagata,Y.,et al.: "A 6-kb upstream region of the human transthyretin gene van direct developmental tissue-specific, and quantitatively normal expression in transgenic mouse." J Biochem. 117. 169-175 (1995)

[文献書誌] Kitamura,D.,et al.: "Molecular cloning and characterization of mouse HS1." Biochem Biophys Res Commun.208. 1137-1146 (1995)

[文献書誌] Yagui,K.,et al.: "Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin." Eur J Endocrinol. 132. 487-496 (1995)

[文献書誌] Hishido,K.,et al.: "Copy-dependent and position-independent expression of rat aldolase A gene." J Biochem. 118. 601-606 (1995)

1995 年度実績報告書

勝木元也東京大学, 医科学研究所, 教授 (20051732)