1994 Fiscal Year Annual Research Report

がん遺伝子・がん抑制遺伝子機能の個体レベルでの解析

Research Project

Project/Area Number	06283231
Research Institution	Kumamoto University
Principal Investigator	相沢慎一熊本大学, 医学部, 教授 (60073011)
Keywords	FAK / mos / 相同組換え / ES細胞 / 中胚葉 / 細胞運動 / lanellipodia / microspikes
Research Abstract	1.胚性未分化細胞での相同組換えによりFAK欠損マウスを作製し、FAKが細胞-細胞外マトリックス相互作用に果たす役割について解析した。FAK欠損胚性未分化細胞はin vitro,in vivoで3胚葉由来の各種細胞に分化し、分化能の欠損は認められなかった。FAK欠損胚は着床し嚢胚形成を開始するが、胚発生8日目前後に異常胚となり発生を停止した。異常は中胚葉に特徴的で、その欠乏によると想定された。しかし中胚葉の各種細胞の分化は認められ、各種分化マーカーの発現を調べたところ、中胚葉細胞の分化能自体の欠損は認められなかった。そこで細胞を培養し、細胞の運動能を計測したところ、運動速度が約半分に低下し、かつpolarな運動形態を示さず、non-polarな形態のまま移動することが明らかとなった。そこで細胞骨格系、細胞-基質接着点の異常を調べたところ、弱いclose contactの形成は起こるがfocal adhesionの形成が起こらず、この為細胞は正常細胞で認められる移動方向のみならず、全ての方向にlamellipodia,ruffles,microspikesを出した状態に留まっていいることが明かとなった。この状態はv-Srcによる細胞癌化に際しての細胞変化と類似し、v-SrcによるFAKリン酸化の高進は、FAK不活性化である可能性を示唆した。 2.先にc-mos欠損マウスを作製し、mosは成熟未受精卵をMII期に安定に停止し、単為発生抑制に働いていることを明らかにした。単為発生は卵巣腫瘍の発症に密接な関連があり、実際c-mos欠損マウスでは卵巣テラトーマが高発する。ヒト卵巣腫瘍のモデルとして卵巣腫瘍発症に至る過程を明らかにした。

Research Products
(17 results)

All Other

All Publications (17 results)

[Publications] Umemori,H.: "Initial events of myelination involve Fyn tyrosine kinase signalling." Nature. 367. 572-576 (1994)
[Publications] Kubo,S.: "A novel form of self tolerance dictated in the thymus of transgenic mice with autoreactive TCRa and b chain genes." Internatl.Immunol.6. 593-602 (1994)
[Publications] Hashimoto,N.: "Parthenogenetic activation of oocytes,but normal spermatogenesis and somatic cell growth,by c-mos-deficiency in mice." Nature. 370. 68-71 (1994)
[Publications] Yagi,T.: "Fyn expression during neurogenesis in mouse embryos." Oncogene. 9. 2433-2440 (1994)
[Publications] Tanaka,N.: "Cellular commitment to oncogene-induced transformation or apoptosisis dependent on the transcription factor IRF-1." Cell. 77. 829-839 (1994)
[Publications] Kohmura,N.: "A novel non-receptor tyrosine kinase,srm;cloning and targeted disruption." Mol.Cell.Biol.14. 6915-6925 (1994)
[Publications] Ishizaki,K.: "Increased UV-induced SCEs in p53-deficient mouse cells." Int.J.Cancer. 58. 254-257 (1994)
[Publications] Tamemoto,H.: "Targeted disruption of the insulin receptor substrate-1 gene results in insulin resistance and growth retardation." Nature. 372. 182-186 (1994)
[Publications] Nada,S.: "Identification of major tyrosine-phosphorylated proteins in Csk-deficient cells." Oncogene. 9. 3571-3578 (1994)
[Publications] Aizawa,S.: "Non-receptor tyrosine kinases in mammalian neurogenesis." Proceedings of the 24h International Symposium of the Princess Takamatsu Cancer Research Fund.323-337 (1994)
[Publications] Sakimura,K.: "Reduced hippocampalLTP and spatiallearning inmice lacking NMDA receptor el subunit." Nature. (in press). (1994)
[Publications] Yoshida,M.: "A new strategy of gene-trapping in ES cells using 3′RACE." Transgenic Research. (in press). (1994)
[Publications] Ilic,D.: "Focal adhesion kinase is not essential for in vitro and in vivo differentiation of ES cells." Biochem.Biophys.Res.Commun.(in press). (1994)
[Publications] Tojo,H.: "Targeted Disruption of the neurotrophin-3 gene with lac Z induces loss of trk C-positive neurons in sensory ganglia but not in spinal cords" Brain Research.669. 163-175 (1995)
[Publications] Hu,L.: "P53 controls proliferation of early B lineage cells by a p21 (WAF1/CIP1)-independent pathway." Biochem.Biophys.Res.Commun.206. 948-954 (1995)
[Publications] Jane.A.Gross.: "Control of Lymphopoiesis by p50csk,a Regulatory Protein Tyrosine Kinase." Exp.Med.181. 463-473 (1995)
[Publications] 相沢慎一: "ジーンターゲテイング:ES細胞を用いた変異マウスの作製バイオマニュアルシリーズ8" 羊土社, 174 (1994)

1994 Fiscal Year Annual Research Report

がん遺伝子・がん抑制遺伝子機能の個体レベルでの解析

Principal Investigator

相沢 慎一 熊本大学, 医学部, 教授 (60073011)

Research Products

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

[Publications] Kubo,S.: "A novel form of self tolerance dictated in the thymus of transgenic mice with autoreactive TCRa and b chain genes." Internatl.Immunol.6. 593-602 (1994)

[Publications] Hashimoto,N.: "Parthenogenetic activation of oocytes,but normal spermatogenesis and somatic cell growth,by c-mos-deficiency in mice." Nature. 370. 68-71 (1994)

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

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

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

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

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

[Publications] Nada,S.: "Identification of major tyrosine-phosphorylated proteins in Csk-deficient cells." Oncogene. 9. 3571-3578 (1994)

[Publications] Aizawa,S.: "Non-receptor tyrosine kinases in mammalian neurogenesis." Proceedings of the 24h International Symposium of the Princess Takamatsu Cancer Research Fund.323-337 (1994)

[Publications] Sakimura,K.: "Reduced hippocampalLTP and spatiallearning inmice lacking NMDA receptor el subunit." Nature. (in press). (1994)

[Publications] Yoshida,M.: "A new strategy of gene-trapping in ES cells using 3′RACE." Transgenic Research. (in press). (1994)

[Publications] Ilic,D.: "Focal adhesion kinase is not essential for in vitro and in vivo differentiation of ES cells." Biochem.Biophys.Res.Commun.(in press). (1994)

[Publications] Tojo,H.: "Targeted Disruption of the neurotrophin-3 gene with lac Z induces loss of trk C-positive neurons in sensory ganglia but not in spinal cords" Brain Research.669. 163-175 (1995)

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

[Publications] Jane.A.Gross.: "Control of Lymphopoiesis by p50csk,a Regulatory Protein Tyrosine Kinase." Exp.Med.181. 463-473 (1995)

[Publications] 相沢慎一: "ジーンターゲテイング:ES細胞を用いた変異マウスの作製 バイオマニュアルシリーズ8" 羊土社, 174 (1994)

相沢慎一熊本大学, 医学部, 教授 (60073011)

[Publications] 相沢慎一: "ジーンターゲテイング:ES細胞を用いた変異マウスの作製バイオマニュアルシリーズ8" 羊土社, 174 (1994)