1996 年度実績報告書

発生に関わる調節分子の全胚における発現・機能の発生工学的解析

研究課題

研究課題/領域番号	08307001
応募区分	総合
研究機関	島根医科大学
研究代表者	大谷浩島根医科大学, 医学部, 教授 (20160533)
研究分担者	山田源鹿児島大学, 工学部, 助教授 (80174712) 南康博神戸大学, 医学部, 助教授 (70229772) 高橋直樹奈良先端科学技術大学院大学, 教授 (30179501) 阪上洋行東北大学, 医学部, 助手 (90261528) 饗場篤東京大学, 医科研, 助教授 (20271116)
キーワード	子宮外発生法 / 組織形成 / K-ras遺伝子 / CaMキナーゼ / 形態形成 / ホメオボックス遺伝子 / 受容体型チロシンキナーゼ / ノックアウトマウス
研究概要	1)子宮外発生法により人工的水頭症を作成し発生病理を検討した。同法によりLIFおよび機能的腫瘍細胞をマウス胎児内に注入し、それぞれ大脳皮質、副腎等の組織形成に及ぼす効果を検索する系を確立した。また同法による遺伝子、抗体等の効率的導入法を検討した。(大谷) 2)H-rasおよびN-ras遺伝子欠損マウスは外見上、正常に発生、成長したことから、両遺伝子はマウスの正常発生に必須ではないことがわかった。一方、K-ras遺伝子欠損マウスは胎児期致死で、心筋細胞の増殖に異常があると考えられた。また、racl遺伝子欠損マウスは胎児期致死であることがわかった。(饗場) 3)神経発達の過程におけるCaMキナーゼの機能を解明する目的で、胎生期脳cDNAライブラリーより1490アミノ酸残基、推定分子量160kDaよりなるCaMキナーゼの単離に成功し、本酵素が胎生期神経系に豊富に発現することをin situハイブリダイゼーション法を用いて明らかにした。(阪上) 4)哺乳類の形態形成過程の分子レベルでの理解を目的として、Hox遺伝子の新しい標的遺伝子mmabを単離しその発現パターンを明らかにした。また新しいホメオボックス遺伝子としてDbxなどの遺伝子をクローン化した。(高橋) 5)ショウジョウバエの神経系発生過程において特異的に発現する新規受容体型チロシンキナーゼDnrkの遺伝子クローニング及び機能解析を行った。更に、Dnrkのマウス相同分子Ror1,2の遺伝子クローニングに成功し、それらの胚発生過程における発現を明らかにした。(南) 6)未分化で多分化能を有する神経堤細胞集団による複雑な顔面-頭部構造の形成過程を明らかにするため、ホメオボックス遺伝子グ-スコイドの機能解析を発展させ、ノックアウトマウスは頭部顔面形成期に嗅覚系、口腔系、咽頭系に異常が生じ生後死亡することを明らかにした。(山田)

研究成果
(25件)

すべてその他

すべて文献書誌 (25件)

[文献書誌] Hashimoto,R.: "Selective translocation of different markers in the ante-and retrograde pathways between the Golgi apparatus and the rough endoplasmic reticulum in a hybridoma cell line." Ann.Anat.179 (in press). (1997)
[文献書誌] Sekimoto,H.: "Developmental analysis of chlorambucil-induced occipital bleds in mice." Cong.Anom.37 (in press). (1997)
[文献書誌] Moriyama,K.: "Degenerative hairlets on the vestibular sensory cells in mutant bustling (BUS/Idr) mice." Acta Otolaryngol.(Stockh). 117. 20-24 (1997)
[文献書誌] Oguni,M.: "Immunohistochemical study of 28-kD heat shock protein in the lens of young human embryos." Ophthalmic Res.28. 270-274 (1996)
[文献書誌] Moriyama,K.: "Occurrence of craniofacial anomalies and liver tumor in transgenic mice expressing osteoblast-specific factor-1 (OSF-1) gene." Transgenics. 2. 69-78 (1996)
[文献書誌] Hatta,T.: "In vivo analysis of RGD-sequence dependent cortical histogenesis in mouse telencephalon." Shimane J.Med.Sci.14. 1-6 (1995/96)
[文献書誌] Yamaguchi,H.: "Dopamine D2 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituitary." Genes to Cells. 1. 253-268 (1996)
[文献書誌] Sakagami,H.: "Immunohistochemical localization of Ca2+/calmodulin-dependent protein kinase IV in the the mature and deveoping rat retina." Brain Res.719. 154-160 (1996)
[文献書誌] Ji,R.-R.: "Ca2+/calmodulin-dependent protein kinase type IV in dorsal root gangion:colocalization with peptides,axonal transport and effect of axotomy." Brain Res.721. 167-173 (1996)
[文献書誌] Sawamura,Y.: "Localization of mRNA for Ca2+/calmodulin-dependent protein kinase I in the brain of developing and mature rats." Brain Res.706. 259-266 (1996)
[文献書誌] Ito,Y.: "Enhanced gene expression for phosphatidylinositol 3-kinase in the hypoglossal motoneurons following axonal crush." Mol.Brain Res.37. 329-332 (1996)
[文献書誌] Shoji,H.: "Regionalized expression of the Dbx family homeobox genes in the embryonic CNS of the mouse." Mech.Dev.56. 25-39 (1996)
[文献書誌] Minami,Y.: "Role of protein-tyrosine kinases in stress signaling." J.Deut.Sci.5. 11-14 (1996)
[文献書誌] Yamada,G.: "Nasal and pharyngeal abnormalities caused by the mouse Goosecoid gene mutation." BBRC. (in press). (1997)
[文献書誌] Yamada,G.: "Metal Composition and Histological Analysis of the Rat Bones from Space Shuttle." Life Sciences. 60. 635-642 (1997)
[文献書誌] Yamada,G.: "Evaluation of cellular responses to growth factors and collagen treated materials by RNA-in situ hybridization." Pharmaceutical Sci.2. 185-188 (1996)
[文献書誌] Sugimura,K.: "Th1/Th2 response profiles to the major allergens,Cry j1 and Cry j2 from Japanese cedar pollen." Allergy. 51. 732-740 (1996)
[文献書誌] Yamada,G.: "Senescence-accelerated mouse (SAM) displays aberrant bone metal composition." Pharmaceutical Sci.2. 305-306 (1996)
[文献書誌] Saegusa,H.: "Targeted disruption in the mouseHoxc-4 locus results in axial skelton homeosis and malformation of the xiphoid process." Dev.Biol.174. 55-64 (1996)
[文献書誌] Qin,S.: "Syk kinase-dependent and independent signaling cascades in B cells elicited by osmotic and oxidative stresses." J,Biol.Chem.(in press). (1997)
[文献書誌] Oishi,I.: "A novel Drosophila receptor tyrosine kinase expressed specifically in nervous system:unique structural features and implication in developmental signaling." J,Biol.Chem.(in press). (1997)
[文献書誌] Adachi,M.: "Interleukin-2 induces tyrosine phosphorylation of SHP-2 through IL-2 receptor β chain." Oncogene. (in press). (1997)
[文献書誌] Ueno,N.: "Identification of a novel Drosophila protein kinase highly homologous to protein kinase N (PKN)." Biochem.Biophys.Res.Commun.(in press). (1997)
[文献書誌] Adachi,M.: "Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor βc chain." Blood. 88. 4118-4123 (1996)
[文献書誌] Hashiguchi,S.: "Immuno-dominance of seven regions of a major allergen,Cry j2 from Japanese cedar pollen for T cell immunity." Allergy. 51. 621-632 (1996)

1996 年度 実績報告書

発生に関わる調節分子の全胚における発現・機能の発生工学的解析

研究代表者

大谷 浩 島根医科大学, 医学部, 教授 (20160533)

研究成果

[文献書誌] Hashimoto,R.: "Selective translocation of different markers in the ante-and retrograde pathways between the Golgi apparatus and the rough endoplasmic reticulum in a hybridoma cell line." Ann.Anat.179 (in press). (1997)

[文献書誌] Sekimoto,H.: "Developmental analysis of chlorambucil-induced occipital bleds in mice." Cong.Anom.37 (in press). (1997)

[文献書誌] Moriyama,K.: "Degenerative hairlets on the vestibular sensory cells in mutant bustling (BUS/Idr) mice." Acta Otolaryngol.(Stockh). 117. 20-24 (1997)

[文献書誌] Oguni,M.: "Immunohistochemical study of 28-kD heat shock protein in the lens of young human embryos." Ophthalmic Res.28. 270-274 (1996)

[文献書誌] Moriyama,K.: "Occurrence of craniofacial anomalies and liver tumor in transgenic mice expressing osteoblast-specific factor-1 (OSF-1) gene." Transgenics. 2. 69-78 (1996)

[文献書誌] Hatta,T.: "In vivo analysis of RGD-sequence dependent cortical histogenesis in mouse telencephalon." Shimane J.Med.Sci.14. 1-6 (1995/96)

[文献書誌] Yamaguchi,H.: "Dopamine D2 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituitary." Genes to Cells. 1. 253-268 (1996)

[文献書誌] Sakagami,H.: "Immunohistochemical localization of Ca2+/calmodulin-dependent protein kinase IV in the the mature and deveoping rat retina." Brain Res.719. 154-160 (1996)

[文献書誌] Ji,R.-R.: "Ca2+/calmodulin-dependent protein kinase type IV in dorsal root gangion:colocalization with peptides,axonal transport and effect of axotomy." Brain Res.721. 167-173 (1996)

[文献書誌] Sawamura,Y.: "Localization of mRNA for Ca2+/calmodulin-dependent protein kinase I in the brain of developing and mature rats." Brain Res.706. 259-266 (1996)

[文献書誌] Ito,Y.: "Enhanced gene expression for phosphatidylinositol 3-kinase in the hypoglossal motoneurons following axonal crush." Mol.Brain Res.37. 329-332 (1996)

[文献書誌] Shoji,H.: "Regionalized expression of the Dbx family homeobox genes in the embryonic CNS of the mouse." Mech.Dev.56. 25-39 (1996)

[文献書誌] Minami,Y.: "Role of protein-tyrosine kinases in stress signaling." J.Deut.Sci.5. 11-14 (1996)

[文献書誌] Yamada,G.: "Nasal and pharyngeal abnormalities caused by the mouse Goosecoid gene mutation." BBRC. (in press). (1997)

[文献書誌] Yamada,G.: "Metal Composition and Histological Analysis of the Rat Bones from Space Shuttle." Life Sciences. 60. 635-642 (1997)

[文献書誌] Yamada,G.: "Evaluation of cellular responses to growth factors and collagen treated materials by RNA-in situ hybridization." Pharmaceutical Sci.2. 185-188 (1996)

[文献書誌] Sugimura,K.: "Th1/Th2 response profiles to the major allergens,Cry j1 and Cry j2 from Japanese cedar pollen." Allergy. 51. 732-740 (1996)

[文献書誌] Yamada,G.: "Senescence-accelerated mouse (SAM) displays aberrant bone metal composition." Pharmaceutical Sci.2. 305-306 (1996)

[文献書誌] Saegusa,H.: "Targeted disruption in the mouseHoxc-4 locus results in axial skelton homeosis and malformation of the xiphoid process." Dev.Biol.174. 55-64 (1996)

[文献書誌] Qin,S.: "Syk kinase-dependent and independent signaling cascades in B cells elicited by osmotic and oxidative stresses." J,Biol.Chem.(in press). (1997)

[文献書誌] Oishi,I.: "A novel Drosophila receptor tyrosine kinase expressed specifically in nervous system:unique structural features and implication in developmental signaling." J,Biol.Chem.(in press). (1997)

[文献書誌] Adachi,M.: "Interleukin-2 induces tyrosine phosphorylation of SHP-2 through IL-2 receptor β chain." Oncogene. (in press). (1997)

[文献書誌] Ueno,N.: "Identification of a novel Drosophila protein kinase highly homologous to protein kinase N (PKN)." Biochem.Biophys.Res.Commun.(in press). (1997)

[文献書誌] Adachi,M.: "Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor βc chain." Blood. 88. 4118-4123 (1996)

[文献書誌] Hashiguchi,S.: "Immuno-dominance of seven regions of a major allergen,Cry j2 from Japanese cedar pollen for T cell immunity." Allergy. 51. 621-632 (1996)

1996 年度実績報告書

大谷浩島根医科大学, 医学部, 教授 (20160533)