1997 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 Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	Tokai University
Principal Investigator	池田穰衛東海大学, 総合医学研究所, 教授 (50266467)
Co-Investigator(Kenkyū-buntansha)	垣塚彰大坂バイオサイエンス研究所, 第4研究所, 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) 黒沢良和藤田保健衛生大学, 総合医科学研究所, 教授 (10109259) 金澤一郎東京大学大学院, 医学研究科, 教授 (30110498)
Keywords	神経変性疾患 / トリプレットリピート病 / ハンチントン病 / 小脳変性疾患 / 脊髄性筋萎縮症 / マシャドジュセフ病 / 分子医学 / 歯状核赤核淡蒼球ルイ体萎縮症
Research Abstract	平成9年度の主要研究成果は、神経細胞生存・維持に関わる新規遺伝子機能の同定、さらにCAGリピート病遺伝子の特徴であるポリグルタミン鎖の伸長に着目して、当該ポリペプチドによる細胞毒性(細胞死の誘起)を培養細胞系を用いて明らかにしたこと等である。次に述べる各神経変性疾患遺伝子における研究成果と相まって、神経細胞障害および神経細胞生存・維持に関わる因子の推定と解析系開発の手掛かりが得られたと言える。これらの成果を踏まえて平成10年度には細胞・分子レベルでの解析が進むことが大いに期待される。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遺伝子は神経細胞死の防御およびアポトーシスの抑制に関わる、今まで未同定であった新規の遺伝子である事をラット脳梗塞モデルを用いて明らかにした(池田)。【ハンチントン病】CAGリピート複製産物(大腸菌系)の構造と派生機構を明らかにした(黒沢)。ヒトハンチントン病異常遺伝子トランスジェニックマウスを作出、F2マウスを得てlineを確立した(永津)。ハンチントン病遺伝子座領域の全転写遺伝子地図の構築を完了した(池田)。【歯状核赤核淡蒼球ルイ体萎縮症】遺伝子産物をバキュロウイルスベクターを用いて大量発現させ、タンパクの部分精製に成功(金澤)。CAGリピートを有する部分cDNAの発現による細胞障害を明らかにした(辻)。【マシャド・ジュセフ病】ポリグルタミン鎖長を調節することによって遅発性疾患モデルマウスの作出に成功(垣塚)。精子での正常と異常対立遺伝子の分離比に偏りがあり、CAGリピート数に不安定性が認められた(西澤)。【優性遺伝性小脳皮質変性症および痙性対麻痺】小脳皮質変性症SCA6患者においてCACNL1A4遺伝子のCAGリピートの異常伸長を認めた。また、痙性対麻痺の責任遺伝子が染色体2番に存在する可能性を得た(佐々木)。

Research Products
(24 results)

All Other

All Publications (24 results)

[Publications] Saitoh.Y: "Chromosome microdissection and microcloning" Chromosome Research. 5. 77-80 (1997)
[Publications] Kogi.M: "A novel tamdem repeat sequence location on human chromosome 4p:Isolation and characterization" Genomics. 42. 278-283 (1997)
[Publications] Xu.D.G.: "Elavation of neuronal expression of NAIP redces ischemic damage in the rat hippocampus." Nature Medicine. 3. 997-1004 (1997)
[Publications] Ichikawa.Y: "A Japanese family carrying a novel mutation in the Emery-Dreifuss muscular dystrophy gene." Ann.Neurol.41. 339-402 (1997)
[Publications] Yazawa.I: "Expression of dentatorubral-pallidoluysian atrophy(DRPLA)proteins in patients." Neuroscience Letters. 255. 53-56 (1997)
[Publications] Wang.G: "Machado-Joseph disease gene product identified in lymphocytes and brain." Biochemical and Biophysical Research Communicarions. 233. 476-479 (1997)
[Publications] M.Seimiya: "Identification of POU-class homeobox genes in freshwater sponge and the specific expression of these genes during differentiation." Eur.J.Biochem.243. 27-31 (1997)
[Publications] Y.Akahori: "Nucleotide sequences of all the gamma gene loci of murine immunoglobulin heavy chains." Genomics. 41. 100-104 (1997)
[Publications] Y.Iba: "Expression vectors for introduction of highly diverged sequences into the six complementarity-determining regions of antibody." Gene. 194. 35-46 (1997)
[Publications] Nagatsu.T: "GTP cyclohydrolase I gene,dystonia,juvenile parkinsonism,and Parkinson's disease." J.Neural Transm.Supplement 49. 203-209 (1997)
[Publications] Higashiyama.S: "A novel brain-derived member of the epidormal growth factor family that interacts with Erb B3 and Erb B4." J.Biochem.122. 675-680 (1997)
[Publications] Kobayashi.K: "Controled genetic ablatron by immunotoxin mediated cell targeting." In:Houdebine,L.M.(Ed.),Transgenic Animals:Generation and Use,Harwood Academic Publishers,Amsterdam,. 331-336 (1997)
[Publications] Oyake.M: "Molecular cloning of murine homologue dentatorubral-pallidoluysian atrophy(DRPLA)cDNA:Strong conservation of a polymorphic CAG repeat in the murine gene." Genomics. 40. 205-507 (1997)
[Publications] Matsumine.H: "Localization of a gene for an autosomal recessive form of juvenile parkinsonism to chromosome 6q25.2-27." Am.J.Hum.Genet.60. 588-596 (1997)
[Publications] Ikeuchi.T: "Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome9." Ann.Neuro.41. 432-437 (1997)
[Publications] Hasumoto.K: "Association of expression of mRNA encoding the PGF2a receptor with luteal cell apoptosis in ovaries of pseudopregnant mice." J.Repro.Fertil.109. 45-52 (1997)
[Publications] Suzuki.F: "Cloning,functional expression and tissue distribution of rabbit a 1 d-adrenoc eptor." Biochim.Biophys.Acta. 12323. 6-11 (1997)
[Publications] Watanabe.N: "p140mDia,a mammalian homolog of Dorosophila diaphanous,is a target protein for Rho small GTPas and is a ligand for profilin." EMBO J.16. 3044-3056 (1997)
[Publications] Takiyama.Y: "Machado-Joseph disease:cerebellar ataxia and autonomic dys-function in a patient with the shortest known expanded allele(56 CAG repeat units)of the MJD1 gene." Neurology. 49. 604-606 (1997)
[Publications] Ishikawa.K: "Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1." Am.J.Hum.Genet.61. 336-346 (1997)
[Publications] Liu X.-Z.: "Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene." Nature Genet. 17(in press). (1997)
[Publications] Fukazawa.T: "Dominantly inherited leukodystrophy showing cerebellar deficits and spastic paraparesis:a new entity?" J.Neurol.244. 446-449 (1997)
[Publications] Sasaki.H: "Neuropathological and molecular studies of spinocerebellar ataxia type 6(SCA6)." Acta Neuropathologica. (in press). (1997)
[Publications] Matsuura.T: "Autosomal dominant spastic paraplegia:clinical and genetic studies of a large Japanese pedigree linked to chromosome 2p." J.Neurol.Sci.(in press). (1997)

1997 Fiscal Year Annual Research Report

単一遺伝子異常による神経細胞死

Principal Investigator

池田 穰衛 東海大学, 総合医学研究所, 教授 (50266467)

Research Products

[Publications] Saitoh.Y: "Chromosome microdissection and microcloning" Chromosome Research. 5. 77-80 (1997)

[Publications] Kogi.M: "A novel tamdem repeat sequence location on human chromosome 4p:Isolation and characterization" Genomics. 42. 278-283 (1997)

[Publications] Xu.D.G.: "Elavation of neuronal expression of NAIP redces ischemic damage in the rat hippocampus." Nature Medicine. 3. 997-1004 (1997)

[Publications] Ichikawa.Y: "A Japanese family carrying a novel mutation in the Emery-Dreifuss muscular dystrophy gene." Ann.Neurol.41. 339-402 (1997)

[Publications] Yazawa.I: "Expression of dentatorubral-pallidoluysian atrophy(DRPLA)proteins in patients." Neuroscience Letters. 255. 53-56 (1997)

[Publications] Wang.G: "Machado-Joseph disease gene product identified in lymphocytes and brain." Biochemical and Biophysical Research Communicarions. 233. 476-479 (1997)

[Publications] M.Seimiya: "Identification of POU-class homeobox genes in freshwater sponge and the specific expression of these genes during differentiation." Eur.J.Biochem.243. 27-31 (1997)

[Publications] Y.Akahori: "Nucleotide sequences of all the gamma gene loci of murine immunoglobulin heavy chains." Genomics. 41. 100-104 (1997)

[Publications] Y.Iba: "Expression vectors for introduction of highly diverged sequences into the six complementarity-determining regions of antibody." Gene. 194. 35-46 (1997)

[Publications] Nagatsu.T: "GTP cyclohydrolase I gene,dystonia,juvenile parkinsonism,and Parkinson's disease." J.Neural Transm.Supplement 49. 203-209 (1997)

[Publications] Higashiyama.S: "A novel brain-derived member of the epidormal growth factor family that interacts with Erb B3 and Erb B4." J.Biochem.122. 675-680 (1997)

[Publications] Kobayashi.K: "Controled genetic ablatron by immunotoxin mediated cell targeting." In:Houdebine,L.M.(Ed.),Transgenic Animals:Generation and Use,Harwood Academic Publishers,Amsterdam,. 331-336 (1997)

[Publications] Oyake.M: "Molecular cloning of murine homologue dentatorubral-pallidoluysian atrophy(DRPLA)cDNA:Strong conservation of a polymorphic CAG repeat in the murine gene." Genomics. 40. 205-507 (1997)

[Publications] Matsumine.H: "Localization of a gene for an autosomal recessive form of juvenile parkinsonism to chromosome 6q25.2-27." Am.J.Hum.Genet.60. 588-596 (1997)

[Publications] Ikeuchi.T: "Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome9." Ann.Neuro.41. 432-437 (1997)

[Publications] Hasumoto.K: "Association of expression of mRNA encoding the PGF2a receptor with luteal cell apoptosis in ovaries of pseudopregnant mice." J.Repro.Fertil.109. 45-52 (1997)

[Publications] Suzuki.F: "Cloning,functional expression and tissue distribution of rabbit a 1 d-adrenoc eptor." Biochim.Biophys.Acta. 12323. 6-11 (1997)

[Publications] Watanabe.N: "p140mDia,a mammalian homolog of Dorosophila diaphanous,is a target protein for Rho small GTPas and is a ligand for profilin." EMBO J.16. 3044-3056 (1997)

[Publications] Takiyama.Y: "Machado-Joseph disease:cerebellar ataxia and autonomic dys-function in a patient with the shortest known expanded allele(56 CAG repeat units)of the MJD1 gene." Neurology. 49. 604-606 (1997)

[Publications] Ishikawa.K: "Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1." Am.J.Hum.Genet.61. 336-346 (1997)

[Publications] Liu X.-Z.: "Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene." Nature Genet. 17(in press). (1997)

[Publications] Fukazawa.T: "Dominantly inherited leukodystrophy showing cerebellar deficits and spastic paraparesis:a new entity?" J.Neurol.244. 446-449 (1997)

[Publications] Sasaki.H: "Neuropathological and molecular studies of spinocerebellar ataxia type 6(SCA6)." Acta Neuropathologica. (in press). (1997)

[Publications] Matsuura.T: "Autosomal dominant spastic paraplegia:clinical and genetic studies of a large Japanese pedigree linked to chromosome 2p." J.Neurol.Sci.(in press). (1997)

池田穰衛東海大学, 総合医学研究所, 教授 (50266467)