1995 Fiscal Year Annual Research Report

ヒト型薬理学実験モデルマウスの開発

Research Project

Project/Area Number	07557012
Research Category	Grant-in-Aid for Developmental Scientific Research (B)
Research Institution	Kyushu University
Principal Investigator	勝木元也九州大学, 生体防御医学研究所, 教授 (20051732)
Co-Investigator(Kenkyū-buntansha)	横山峯介三菱化学生命研究所, 生殖室長(主任研究員中尾和貴九州大学, 生体防御医学研究所, 教務員中村健司九州大学, 生体防御医学研究所, 助手 (90253533) 饗場篤九州大学, 生体防除医学研究所, 助手 (20271116)
Keywords	ジーンターゲッティング / 標的遺伝子組換え / 標的遺伝子置換 / セロトニン受容体 / 薬理作用 / 発生工学 / 遺伝子工学 / ES細胞
Research Abstract	動物実験による薬理作用の研究は、ヒト疾患に有効な薬の開発にとって最も重要なものの一つである。ところが、生体に作用する化学物質の薬理作用が、ヒトと動物とで異なる場合がある。すなわち、薬の効き方が動物種によって異なる場合である。なかでも受容体のちがいによって薬理作用が異なる場合も多く認められる。そこでマウスの受容体をヒト型に変換させることができれば、従来不可能であった様々な薬理学的動物実験が可能となるであろう。これまで、計画的には、このような遺伝子変換は困難であったが、最近の遺伝子工学と発生工学とよって計画的に遺伝子を変換したマウス個体を作ることができるようになった。我々は、この方法をさらに一歩進めて、標的とする目的の遺伝子に点突然変異や欠失、またヒトをはじめとする異種遺伝子に置き換える方法の開発に成功した(標的遺伝子置換法)。この方法を、セロトニン受容体1Bに適用し、薬理作用がヒトと異なるマウスを、ヒト型に変換することを試みた。その結果、セロトニン受容体1B遺伝子の標的組換え体ES細胞の単離に成功した。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Yamaguchi,H.,et al.: "Dopamine D2 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituiary." Genes to Cells. in press.
[Publications] Gondo,Y.,et al.: "A novel positive detection system of in vivo mutations in rpsL(strA)transgenic mice." Mutation Res. in press.
[Publications] 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)
[Publications] 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)
[Publications] Honda,H.,et al.: "Increased pyrosine-phosphorylation of 55KDa proteins in beta-actin/Tec transgenic mice." Biochem Biophys Res Commun. 206. 287-293 (1995)
[Publications] Tamura,H.,et al.: "Opaque eyes developed in transgenic mice with T-cell receptor δ gene." Invest Ophthalmol Vis Sci. 36. 467-477 (1995)
[Publications] Kano,M.,et al.: "Impaired synapse elimination during cerebellar development in PKCγ mutant mice." Cell. 83. 1223-1231 (1995)
[Publications] Hsia,A.Y.,et al.: "Evidence against a role for metabotropic glutamate receptors in mossy fiber LTP:the use of mutani mice and pharmacological antagonists." Neuropharmacol. 34. 1567-1572 (1995)
[Publications] Yokoyama,M.,et al.: "The creation of mouse models for human diseases associated with reproductive disturbances by in vitro fertilization and embryo transfer." Exp Anim. 44. 139-143 (1995)
[Publications] Yokoyama,M.,et al.: "Conversion of the genetic background of transgenic mice by in vitro fertilization." Exp Anim. 44. 145-150 (1995)
[Publications] Kaneko-Ishino,T.,et al.: "Pegl/Mest imprinted gene on chromosome 6 identified by cDNA subtraction hybridization." Nature Genet. 11. 52-59 (1995)

1995 Fiscal Year Annual Research Report

ヒト型薬理学実験モデルマウスの開発

Principal Investigator

勝木 元也 九州大学, 生体防御医学研究所, 教授 (20051732)

Research Products

[Publications] Yamaguchi,H.,et al.: "Dopamine D2 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituiary." Genes to Cells. in press.

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

[Publications] 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)

[Publications] 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)

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

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

[Publications] Kano,M.,et al.: "Impaired synapse elimination during cerebellar development in PKCγ mutant mice." Cell. 83. 1223-1231 (1995)

[Publications] Hsia,A.Y.,et al.: "Evidence against a role for metabotropic glutamate receptors in mossy fiber LTP:the use of mutani mice and pharmacological antagonists." Neuropharmacol. 34. 1567-1572 (1995)

[Publications] Yokoyama,M.,et al.: "The creation of mouse models for human diseases associated with reproductive disturbances by in vitro fertilization and embryo transfer." Exp Anim. 44. 139-143 (1995)

[Publications] Yokoyama,M.,et al.: "Conversion of the genetic background of transgenic mice by in vitro fertilization." Exp Anim. 44. 145-150 (1995)

[Publications] Kaneko-Ishino,T.,et al.: "Pegl/Mest imprinted gene on chromosome 6 identified by cDNA subtraction hybridization." Nature Genet. 11. 52-59 (1995)

勝木元也九州大学, 生体防御医学研究所, 教授 (20051732)