| Project/Area Number |
03670516
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | The Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
SAKURABA Hitoshi The Tokyo Metropolitan Institute of Medical Science, Department of Clinical Genetics, Research Scientist, 臨床遺伝学研究部門・研究 (60114493)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Satoshi The Tokyo Metropolitan Institute of Medical Science, Department of Clinical Gene, 臨床遺伝学研究部門, 研究員 (00222935)
KASE Ryoichi The Tokyo Metropolitan Institute of Medical Science, Department of Clinical Gene, 臨床遺伝学研究部門, 研究員 (20150203)
ITOH Kohji The Tokyo Metropolitan Institute of Medical Science, Department of Clinical Gene, 臨床遺伝学研究部門, 研究員 (00184656)
OSHIMA Akihiro The Tokyo Metropolitan Institute of Medical Science, Department of Clinical Gene, 臨床遺伝学研究部門, 研究員 (20203763)
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| Project Period (FY) |
1991 – 1993
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| Keywords | gene expression / Fabry disease / alpha-galactosidase / baculovirus / enzyme replacement therapy / confocal laser scanning microscopy / galactosialidosis / protective protein |
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| Research Abstract |
Effors were directed to clarify the pathogenesis of Fabry disease and galactosialidosis and develop the therapy for these diseases by means of gene expression system.
Fabry disease is an X-linked inborn error of glycosphingolipid catabolism resulting from the deficient activity of alpha-galactosidase. The specific alpha-galactosidase mutations that cause the classic or variant Fabry disease phenotypes have been deterined. A variety of mutations, including deletions, nonsense mutations, splicing mutations and amino acid substitutions caused complete deficiency of alpha-galactosidase activity and resulted in the classic form of Fabry manifestations. Single base substitutions between 5'-end and the center of exon 6 led to the residual enzyme activity and variant form of Fabry phenotype. A large amount of human alpha-galactosidase was expressed using recombinant baculovirus/insect cell expression system and a possibility of enzyme replacement therapy for Fabry disease was investigated.
A genetic defect of protective protein causes an systemic disease, galactosialidosis. Expression of human protective protein was established in transformed Chinese hamster ovary cells, and purified protective protein was confirmed to be a multifunctional enzyme protein.
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