| Project/Area Number |
07670913
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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 |
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Principal Investigator |
AOKI Tsugutoshi Toho Univ., 2nd Dept.of Pediatrics, Professor, 第二小児科学教室, 教授 (50057585)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Akira Toho Univ., Dept.of Molecular Biology, Assistant professor, 分子生物学研究室, 講師 (10151599)
YAMAGUCHI Yukitoshi Toho Univ., 2nd Dept.of Pediatrics, Staff, 第二小児科学教室, 助手 (30277339)
KAZAMA Hiromi Toho Univ., 2nd Dept.of Pediatrics, Staff, 第二小児科学教室, 助手 (90224386)
FUJIOKA Yoshimi Toho Univ., 2nd Dept.of Pediatrics, Staff, 第二小児科学教室, 助手 (30256739)
SHIMIZU Norikazu Toho Univ., 2nd Dept.of Pediatrics, Assistant professor, 第二小児科学教室, 講師 (60256740)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | inborn error of copper metabolism / Wilson disease / Menkes disease / P-type ATPase / genotype / phenotype / genotypeとphenotype / 遺伝子解析 |
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| Research Abstract |
To investigate correlation between genotype and phenotype and intracellular copper metabolism of inborn error of copper metabolism, the authors performed gene analysis for Wilson disease patients, and studied intracellular localization of ATP-7A and 7B proteins.
The mutations of ATP-7B in hepatic type (including fluminant type) of Wilson disease were one point dilutions that make frame shift. Truncated proteins must be synthesized from these mutated genes. And we suggest these proteins have no any function as a copper transporter. The patients in neurological and hepatoneurological type of Wilson disease revealed mis sense mutation and exon skipping as a result of point mutations. The mutated protein may be leave some part of function. These results show the possibility 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).
Both of the proteins synthesized from ATP-7A (Menkes disease gene) and ATP-7B (Wilson disease gene) were localized in the trans-Golgi network and post-Golgi vesicular compartment intracllulary. The ATP-7B gene expressed specifically on liver, kidney and brain. And ATP-7A gene expressed on the most of all organs except for liver. We conclude from these results that the copper metabolic function of ATP-7A and 7B must be same intracllulary, and phenotypical difference between Wilson disease and Menkes disease is due to difference of organic localization of these two kind of copper transporting P-type ATPase.
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