1998 Fiscal Year Annual Research Report

単一遺伝子異常による神経細胞死

Research Project

Project/Area Number	09280105
Research Institution	Tokai University
Principal Investigator	池田穣衛東海大学, 総合医学研究所, 教授 (50266467)
Co-Investigator(Kenkyū-buntansha)	佐々木秀直北海道大学, 大学院・医学研究科, 講師 (80281806) 垣塚彰大阪バイオサイエンス研究所, 第4研究部, 部長(研究職) (80204329) 辻省次新潟大学, 脳研究所, 教授 (70150612) 永津俊治藤田保健衛生大学, 総合医科学研究所, 教授 (40064802) 金澤一郎東京大学, 大学院・医学系研究科, 教授 (30110498)
Keywords	神経細胞死 / アポトーシス / ポリグルタミン病 / ハンチントン病 / ダイナミックミューテーション / NAIP / MJD / DRPLA
Research Abstract	平成10年度の特筆すべき成果は、CAGリピート病遺伝子の特徴である伸長ポリグルタミン鎖が細胞核内に凝集体を形成し細胞障害性を示すこと.脊髄性筋萎縮症責任遺伝子産物(NAIP)が生体内において脳神経細胞死を阻止すること等である. 各神経変性疾患遺伝子における研究成果の概要:【脊髄性筋萎縮症】 NAIP遺伝子の強制発現により、脳虚血による脳神経細胞死を阻止できること、NAIPの活性化にプロセシングと細胞核への局在が伴うことを明らかにした(池田). 【ハンチントン病】 CAGリピートに依存し、且つCAGリピート固有の複製が認められる大腸菌の系の開発に成功した(黒沢).ヒトハンチントン病異CAGリピート置換マウスを作出、F2マウスを得てlineを確立した(永津).ミニブタハンチントン変異遺伝子(伸長CAGリピート)を保持するトランスジェニックミニブタを作出した(池田). 【歯状核赤核淡蒼球ルイ体萎縮症】責任遺伝子産物大量発現と、タンパクの精製に成功(金澤).責任遺伝子産物の細胞内局在について、培養細胞の種類,ポリグルタミンの長さによって核内にも細胞質内にも存在しうることを見いだした(辻). 【マシャド・ジョセフ病】ポリグルタミンの核内凝集体が神経細胞死の誘導に極めて重要な役割を果たしていることを明らかにした(垣塚).患者及びトランスジェニックマウスの生殖臓器におけるCAGリピートの動態を解析し、単一精子レベルで最も著明なリピート数のばらつきを認めた(西澤). 【優性遺伝性小脳皮質変性症および痙性対麻痺】優生遺伝性小脳皮質変性症と診断された23家系について、その12家系にSCA6遺伝子のCAGリピートの異常伸長が認められた.さらに,本邦のSCA6には創始者効果のあると思われる結果を得た(佐々木).

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Hadano S,et al: "The primary structure and genomic organaization of five novel transcripts located close to the Huntington's disease gene on human chromosome 4p16.3." DNA Research. 5. 177-186 (1998)
[Publications] Chen.Q,et al: "Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy genes SMN and NAIP." Genomics. 48. 121-127 (1998)
[Publications] Song.J,et al: "Genomic organization and expression of a human gene for Myc-associated zinc finger pritein(MAZ)" J Biol Chem. 273. 20603-20614 (1998)
[Publications] Kobayashi.K,et al: "An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy" Nature. 394. 388-392 (1998)
[Publications] Yasui.Y,et al: "Temperature dependency of the thermodynamic parameters in interactions between hen egg-white lysozyme(HEL)and anti-HEL antibody." J.Biochem. 123. 827-831 (1998)
[Publications] Kubota.T,et al: "Upregulation of nucleobindin expression in human-activated lymphocytes and non-Hodgkins lymphoma." Pathology International. 48. 22-28 (1998)
[Publications] Ishiguro.H,et al: "Identification and charac terization of a novel phorbol ester-responsive DNA sequence in the 5ユ flanking region of the human dopamine b-hydroxylase gene." Journal of Biological Chemistry. 273. 21942-21949 (1998)
[Publications] Cubells.J.F.,et al: "Dopamine b-hydroxylase:two polymorphisms in linkage disequilibrium at the structural gene DBH-associate with biochemical phenotypic variation." Human Genetics. 102. 533-540 (1998)
[Publications] Igarashi.S,et al: "Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch." Nature Genet. 18. 111-117 (1998)
[Publications] Ikeuchi.T,et al: "A novel long and unstable CAG/CTG trinucleotide repeat on chromosome 17q." Genomics. 49. 321-326 (1998)
[Publications] Wellington.C.L.,et al: "Caspase Cleavage of gene products a ssocated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract." Journal of Biological Chemistry. 273. 9158-9167 (1998)
[Publications] Yamaguchi.M,et al: "Retardation of skeletal development and cervical abnormalities in transgenic mice expressing a dominant-negative retinoic acid receptor in chondrogenic cells." Proceeding of National Academy of Science U.S.A. 95. 7491-7496 (1998)
[Publications] Takiyama.Y,et al: "Maternal anticipation in Machado-Joseph disease(MJD):some familial factors independent of the number of CAG repeat units may play a role in genetic anticipation in a Japanese MJD family." J Neurol Sci. 155. 141-145 (1998)
[Publications] Fan D-S,et al: "Prevention of dopaminergic neuron death by adeno-associated virus vector-mediated GDNF gene transfer in rat mesencephalic cells in virto." Neurosci Lett. 243. 61-64 (1998)
[Publications] Sasaki.H,et al: "Neuropathological and molecular studies of spinocerebellar ataxia type 6(SCA6)." Acta Neuropathol. 95. 141-145 (1998)
[Publications] Ikeuchi.T,et al: "A novel long and unstable CAG/CTG trinucleotide repeat on chromosome 17q." Gemomics. 49. 321-326 (1998)

1998 Fiscal Year Annual Research Report

単一遺伝子異常による神経細胞死

Principal Investigator

池田 穣衛 東海大学, 総合医学研究所, 教授 (50266467)

Research Products

[Publications] Hadano S,et al: "The primary structure and genomic organaization of five novel transcripts located close to the Huntington's disease gene on human chromosome 4p16.3." DNA Research. 5. 177-186 (1998)

[Publications] Chen.Q,et al: "Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy genes SMN and NAIP." Genomics. 48. 121-127 (1998)

[Publications] Song.J,et al: "Genomic organization and expression of a human gene for Myc-associated zinc finger pritein(MAZ)" J Biol Chem. 273. 20603-20614 (1998)

[Publications] Kobayashi.K,et al: "An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy" Nature. 394. 388-392 (1998)

[Publications] Yasui.Y,et al: "Temperature dependency of the thermodynamic parameters in interactions between hen egg-white lysozyme(HEL)and anti-HEL antibody." J.Biochem. 123. 827-831 (1998)

[Publications] Kubota.T,et al: "Upregulation of nucleobindin expression in human-activated lymphocytes and non-Hodgkins lymphoma." Pathology International. 48. 22-28 (1998)

[Publications] Ishiguro.H,et al: "Identification and charac terization of a novel phorbol ester-responsive DNA sequence in the 5ユ flanking region of the human dopamine b-hydroxylase gene." Journal of Biological Chemistry. 273. 21942-21949 (1998)

[Publications] Cubells.J.F.,et al: "Dopamine b-hydroxylase:two polymorphisms in linkage disequilibrium at the structural gene DBH-associate with biochemical phenotypic variation." Human Genetics. 102. 533-540 (1998)

[Publications] Igarashi.S,et al: "Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch." Nature Genet. 18. 111-117 (1998)

[Publications] Ikeuchi.T,et al: "A novel long and unstable CAG/CTG trinucleotide repeat on chromosome 17q." Genomics. 49. 321-326 (1998)

[Publications] Wellington.C.L.,et al: "Caspase Cleavage of gene products a ssocated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract." Journal of Biological Chemistry. 273. 9158-9167 (1998)

[Publications] Yamaguchi.M,et al: "Retardation of skeletal development and cervical abnormalities in transgenic mice expressing a dominant-negative retinoic acid receptor in chondrogenic cells." Proceeding of National Academy of Science U.S.A. 95. 7491-7496 (1998)

[Publications] Takiyama.Y,et al: "Maternal anticipation in Machado-Joseph disease(MJD):some familial factors independent of the number of CAG repeat units may play a role in genetic anticipation in a Japanese MJD family." J Neurol Sci. 155. 141-145 (1998)

[Publications] Fan D-S,et al: "Prevention of dopaminergic neuron death by adeno-associated virus vector-mediated GDNF gene transfer in rat mesencephalic cells in virto." Neurosci Lett. 243. 61-64 (1998)

[Publications] Sasaki.H,et al: "Neuropathological and molecular studies of spinocerebellar ataxia type 6(SCA6)." Acta Neuropathol. 95. 141-145 (1998)

[Publications] Ikeuchi.T,et al: "A novel long and unstable CAG/CTG trinucleotide repeat on chromosome 17q." Gemomics. 49. 321-326 (1998)

池田穣衛東海大学, 総合医学研究所, 教授 (50266467)