1998 Fiscal Year Annual Research Report

遺伝性神経変性疾患におけるトリプレットリピート伸張

Research Project

Project/Area Number	09044357
Research Institution	National Research Institute for Child Health and Development
Principal Investigator	山田正夫国立小児病院, 小児医療研究センター先天異常研究部, 部長 (40124218)
Co-Investigator(Kenkyū-buntansha)	POTTER Nich University of Tennessee Medical Center, Assistant BURKE James Duke University Medical Center, Division, Assistant 奥山虎之国立小児病院, 奇形研究室, 室長宮下俊之国立小児病院, 遺伝染色体研究室, 室長 (60174182)
Keywords	トリプレットリピート伸長病 / ポリグルタミン / アポトーシス / 歯状核赤核淡蒼球ルイ体萎縮症 / DRPLA / ハンチントン舞踏病 / 遺伝病 / 神経変性疾患
Research Abstract	1. 臨床症状からハンチントン舞踏病と診断されていたが、HD遺伝子のCAGリピートの伸張を伴っていなかった米国の患者についてDNAを検査し、7家系11名でDRPLAと同定した。またユダヤ人で中間体リピートを検出した。これらの家系DNAについて、山田の研究室でハプ口タイプを解析し、起源などを明らかにした。 2. CAGリピート伸張病における神経細胞死の機構について、凝集体形成およびアポトーシスの関与が指摘されつつある。この方面の研究情報を交換し、それぞれの研究室の最新結果を交換するなどして、神経細胞死機構の研究を進めた。特に微小凝集体(あるいは凝集性)が重要な鍵であること、またCaspase-8の早期の関与を明らかにでき、この分野の迅速な発展に大きく貢献した。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Miyashita,T.: "Intracellular aggregate formation of dentatorubral-pallidoluysian atrphy(DRPLA)protein with the extended polyglutamine." Biochemical and Biophysical Research Communications. 249(1). 96-102 (1998)
[Publications] Miyashita,T.: "Investigation of glucocorticoid-induced apoptotic pathway:processing of caspase-6 but not caspase-3." Cell Death and Differentiation. 5(12). 1034-1041 (1998)
[Publications] Takayama,S.: "Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues tumor cell lines." Cancer Research. 58(14). 3116-3131 (1998)
[Publications] Okuyama,T.: "Efficent Fas-ligand gene expression in rodent liver after intravenous injection of a recombinant adenovirus by the use of a Cre-mediated switching system." Gene Therapy. 5(8). 1047-1053 (1998)
[Publications] Okuyama,T.: "Fas-mediated apoptosis is involved in the elimination of gene-transduced hepatocytoes with E1/E3-deleted adenoviral vectors." Journal of Gastroenterology and Hepatology. 13(suppl.). S113-118 (1998)
[Publications] Okuyama,T.: "Hepatocyte-specific gene expression by a recombinant adeno-associated virus vector carrying apolipooprotein E enhancer and α1-antitrypsin promoter." Gene Therapy and Molecular Biology. 3. 67-74 (1998)
[Publications] Li,X-K.: "Prolonged survival of rat liver allografts transfected with Fas ligand-expressing plasmid." Transplantation. 66(11). 1416-1423 (1998)
[Publications] Azuma,N.: "Missense mutation at the C terminus of the PAX6 gene in ocular anterior segment anomalies." Investigative Ophthalmology and Visual Science. 39(5). 828-830 (1998)
[Publications] Azuma,N.: "Missense Mutations in the PAX6 gene in aniridia." Investigative Ophthalmology and Visual Science. 39(13). 2524-2528 (1998)
[Publications] Yuan,ZR.: "Mutational analysis of the Jagged 1 gene in Alagille syndrome families." Human Molecular Genetics. 7(9). 1363-1369 (1998)
[Publications] Sakai,K.: "The genomic organization of the human corticotropin-releasing factor type-1 receptor." Gene. 219(1-2). 125-130 (1998)

1998 Fiscal Year Annual Research Report

遺伝性神経変性疾患におけるトリプレットリピート伸張

Principal Investigator

山田 正夫 国立小児病院, 小児医療研究センター先天異常研究部, 部長 (40124218)

Research Products

[Publications] Miyashita,T.: "Intracellular aggregate formation of dentatorubral-pallidoluysian atrphy(DRPLA)protein with the extended polyglutamine." Biochemical and Biophysical Research Communications. 249(1). 96-102 (1998)

[Publications] Miyashita,T.: "Investigation of glucocorticoid-induced apoptotic pathway:processing of caspase-6 but not caspase-3." Cell Death and Differentiation. 5(12). 1034-1041 (1998)

[Publications] Takayama,S.: "Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues tumor cell lines." Cancer Research. 58(14). 3116-3131 (1998)

[Publications] Okuyama,T.: "Efficent Fas-ligand gene expression in rodent liver after intravenous injection of a recombinant adenovirus by the use of a Cre-mediated switching system." Gene Therapy. 5(8). 1047-1053 (1998)

[Publications] Okuyama,T.: "Fas-mediated apoptosis is involved in the elimination of gene-transduced hepatocytoes with E1/E3-deleted adenoviral vectors." Journal of Gastroenterology and Hepatology. 13(suppl.). S113-118 (1998)

[Publications] Okuyama,T.: "Hepatocyte-specific gene expression by a recombinant adeno-associated virus vector carrying apolipooprotein E enhancer and α1-antitrypsin promoter." Gene Therapy and Molecular Biology. 3. 67-74 (1998)

[Publications] Li,X-K.: "Prolonged survival of rat liver allografts transfected with Fas ligand-expressing plasmid." Transplantation. 66(11). 1416-1423 (1998)

[Publications] Azuma,N.: "Missense mutation at the C terminus of the PAX6 gene in ocular anterior segment anomalies." Investigative Ophthalmology and Visual Science. 39(5). 828-830 (1998)

[Publications] Azuma,N.: "Missense Mutations in the PAX6 gene in aniridia." Investigative Ophthalmology and Visual Science. 39(13). 2524-2528 (1998)

[Publications] Yuan,ZR.: "Mutational analysis of the Jagged 1 gene in Alagille syndrome families." Human Molecular Genetics. 7(9). 1363-1369 (1998)

[Publications] Sakai,K.: "The genomic organization of the human corticotropin-releasing factor type-1 receptor." Gene. 219(1-2). 125-130 (1998)

山田正夫国立小児病院, 小児医療研究センター先天異常研究部, 部長 (40124218)