2000 Fiscal Year Annual Research Report

哺乳類脳で多様化した遺伝子の探索

Research Project

Project/Area Number	11878134
Research Institution	Osaka University
Principal Investigator	八木健大阪大学, 細胞生体工学センター, 教授 (10241241)
Keywords	Fyn / CNR / カドヘリン / 情動行動 / 遺伝子クラスター / 多様化 / シナプス / 神経回路形成
Research Abstract	我々は、現在までに哺乳類脳で多様化した遺伝子群としてCNRファミリーの単離に成功した。興味深いことに、このCNRファミリーは免疫系のT細胞受容体や免疫グロブリンと類似した遺伝子クラスターを形成していた。このCNRファミリーの発現制御機構を明らかにする目的で、可変領域と定常領域の連結機構の解析を行った。その結果、興味深いことに異なった染色体上の可変領域と定常領域が連結するトランスの遺伝子産物が成体マウス脳で約10%存在すること、またこのトランスの産物がマウス脳の発達にともなって増加することが明らかとなった。またさらに驚いたことに、CNR3についてのmRNAの配列を解析した結果、成体マウス脳において突然変異が蓄積されていることが明らかとなった。この突然変異率はEカドヘリンとの間で統計的に有意であり、また突然変異率ごとのクローンの分布が、CNR3については正規分布とならないことより、体細胞レベルでの突然変異の蓄積が示唆された。この突然変異は脳の発達に伴い増加すること、トランスの遺伝子産物において突然変異率が統計的有意に高いことが明かとなった。この体細胞レベルでの突然変異のアミノ酸配列変換への影響を調べたところ、興味深いことに、CNRの特異的認識に重要であると考えられる第一カドヘリン領域のみで、アミノ酸配列変換が高いことが明らかとなり、突然変異の蓄積とシナプス結合の特異性変化との関連性が示唆された。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Sugino H.: "Genomic organization of the family of CNR cadherin genes in mice and humans."Genomics. 63. 75-87 (2000)
[Publications] Yamazaki Y.: "In vivo gene transfer to mouse spermatogenic cells using green fluorescent protein as a marker."Journal of Experimental Zoology. 286. 212-218 (2000)
[Publications] Yagi T.: "Cadherin superfamily genes : functions, genomic organization, and neurologic diversity."Genes & Development. 14. 1169-1180 (2000)
[Publications] Shima Y.: "Changes in circadian period and morphology of the hypothalamic suprachiasmatic nucleus in fyn kinase-deficient mice."Brain Research. 870. 36-43 (2000)
[Publications] Kitazawa H.: "Dynamic characteristics and adaptability of reflex eye movements of Fyn kinase-deficient mice."Neuroscience Letter. 280. 179-182 (2000)
[Publications] Seiwa C.: "Fyn tyrosine kinase participates in the compact myelin sheath central nervous system."Neuroscience Research. 37. 21-31 (2000)
[Publications] Huang G-Z.: "Involvement of complexin II in synaptic plasticity in the CA1 region of the hippocampus : The use of complexin II-lacking mice."Japan Journal Pharmacology. 84. 179-187 (2000)
[Publications] Kawase E.: "Mouse embryonic stem (ES) cell lines established from neuronal cell-derived cloned blastocysts."Genesis. 28. 156-163 (2000)
[Publications] Mei Z-t.: "Impairment of conditioned avoidance response in Fyn-kinase deficient mice."China Journal Neuroscience. 16. 293-298 (2000)
[Publications] Hirayama T.: "Somatic mutations of synaptic cadherin (CNR family) transcripts in the nervous system."Genes to Cells,. (in press). (2001)
[Publications] Miyakawa T.: "Differential effect of Fyn tyrosine kinase deletion on offensive and defensive aggression."Molecular Brain Research,. (in press). (2001)
[Publications] Yagi T.: "Ethanol sensitivity and molecular function of Fyn tyrosine kinase."Ethanol and Intracellular signalling : From Molecules to Behavior""CSR incorporated, in Washington, DC.. (2001)
[Publications] Takei Y.: "Two novel CNRs from the CNR gene cluster have molecular features distinct from those of CNR1 to 8"Genomics, in press. 73. (2001)
[Publications] Nakahara J.: "Myelin basic protein is necessary for the regulation of myelin-associated glycoprotein expression in mouse oligodendroglia."Neuroscience Letter. 298(3). 163-166 (2001)
[Publications] Nakamura K.: "Enhancement of hippocampal LTP, reference memory and sensorimotor gating in mutant mice lacking a telencephalon-specific cell adhesion molecule."Euro Journal Neuroscience. 13(1). 179-189 (2001)
[Publications] 八木健: "ジーンターゲティングの最新技術"羊土社. 233 (2000)

2000 Fiscal Year Annual Research Report

哺乳類脳で多様化した遺伝子の探索

Principal Investigator

八木 健 大阪大学, 細胞生体工学センター, 教授 (10241241)

Research Products

[Publications] Sugino H.: "Genomic organization of the family of CNR cadherin genes in mice and humans."Genomics. 63. 75-87 (2000)

[Publications] Yamazaki Y.: "In vivo gene transfer to mouse spermatogenic cells using green fluorescent protein as a marker."Journal of Experimental Zoology. 286. 212-218 (2000)

[Publications] Yagi T.: "Cadherin superfamily genes : functions, genomic organization, and neurologic diversity."Genes & Development. 14. 1169-1180 (2000)

[Publications] Shima Y.: "Changes in circadian period and morphology of the hypothalamic suprachiasmatic nucleus in fyn kinase-deficient mice."Brain Research. 870. 36-43 (2000)

[Publications] Kitazawa H.: "Dynamic characteristics and adaptability of reflex eye movements of Fyn kinase-deficient mice."Neuroscience Letter. 280. 179-182 (2000)

[Publications] Seiwa C.: "Fyn tyrosine kinase participates in the compact myelin sheath central nervous system."Neuroscience Research. 37. 21-31 (2000)

[Publications] Huang G-Z.: "Involvement of complexin II in synaptic plasticity in the CA1 region of the hippocampus : The use of complexin II-lacking mice."Japan Journal Pharmacology. 84. 179-187 (2000)

[Publications] Kawase E.: "Mouse embryonic stem (ES) cell lines established from neuronal cell-derived cloned blastocysts."Genesis. 28. 156-163 (2000)

[Publications] Mei Z-t.: "Impairment of conditioned avoidance response in Fyn-kinase deficient mice."China Journal Neuroscience. 16. 293-298 (2000)

[Publications] Hirayama T.: "Somatic mutations of synaptic cadherin (CNR family) transcripts in the nervous system."Genes to Cells,. (in press). (2001)

[Publications] Miyakawa T.: "Differential effect of Fyn tyrosine kinase deletion on offensive and defensive aggression."Molecular Brain Research,. (in press). (2001)

[Publications] Yagi T.: "Ethanol sensitivity and molecular function of Fyn tyrosine kinase."Ethanol and Intracellular signalling : From Molecules to Behavior""CSR incorporated, in Washington, DC.. (2001)

[Publications] Takei Y.: "Two novel CNRs from the CNR gene cluster have molecular features distinct from those of CNR1 to 8"Genomics, in press. 73. (2001)

[Publications] Nakahara J.: "Myelin basic protein is necessary for the regulation of myelin-associated glycoprotein expression in mouse oligodendroglia."Neuroscience Letter. 298(3). 163-166 (2001)

[Publications] Nakamura K.: "Enhancement of hippocampal LTP, reference memory and sensorimotor gating in mutant mice lacking a telencephalon-specific cell adhesion molecule."Euro Journal Neuroscience. 13(1). 179-189 (2001)

[Publications] 八木健: "ジーンターゲティングの最新技術"羊土社. 233 (2000)

八木健大阪大学, 細胞生体工学センター, 教授 (10241241)