| Project/Area Number |
08670919
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Toho University School of Medicine |
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Principal Investigator |
SHIMIZU Norikazu Toho Univ., 2nd Dept.of Pediatrics, Assistant professor, 医学部・第2小児科学教室, 講師 (60256740)
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| Co-Investigator(Kenkyū-buntansha) |
HEMMI Hiromich Toho Univ., Dept.of Molecular Biology, Associate professoe, 医学部・分子生物学研究室, 助教授 (90165514)
YAMAGUCHI Yukitoshi Toho Univ., 2nd Dept.of pediatrics, Assistant professor, 医学部・第2小児科学教室, 講師 (30277339)
藤岡 芳実 東邦大学, 医学部・第二小児科学教室, 助手 (30256739)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Inborn error of copper metabolism / copper transporting P-type A Tpase / Wilson disease / Menkes disease / gene analysis / intracellular localization |
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| Research Abstract |
1.The intracellular localization of Menkes disease gene (ATP-7A) protein and Wilson disease gene (ATP-7B) protein
Both of the proteins synthesized from ATP-7A and 7B were localized in the trans-Golgi network under steady conditions. An increase in the intracellular copper concentration resulted in the rapid movement of these proteins to a cytoplasmic vesicular compartment. This copper-specific cellular redistribution of ATP-7A and 7B protein is a reversible process that occurs independent of new protein (small vesicles of copper transport).
2.The corelationship between genotype and clinical features in Wilson disease
The most of mutations of ATP-7B in hepatic type (including fulminant type) of Wilson disease were one point dilutions that make frame shift. Truncated proteins must be synthesized from these mutated genes. And these proteins may have no any function as a Copper transporter. The patients who have neurologic symptom revealed missense mutation and exon skipping. These mutated protein can be leave some part of function. These results suggest that difference of phenotypes of Wilson disease depend on functional levels of Wilson disease protein. And protein function is regulated by types of gene mutations (genotype). The sever impairment of ATP-7B,such one base deletion would remove function, leads to sever liver dysfunction, such as fulminant type of Wilson disease.
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