Role of dystrophin-related protein in the pathogenesis of Duchenne muscular dystrophy.
| Project/Area Number |
04670508
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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 |
神経内科学
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| Research Institution | Institute of Molecular and Cellular Biosciences, The University of Tokyo |
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Principal Investigator |
ISHIURA Shoichi Institute of Molecular and Cellular Biosciences, The University of Tokyo, Associate Professor, 分子細胞生物学研究所, 助教授 (10158743)
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| Co-Investigator(Kenkyū-buntansha) |
TAGAWA Kazuhiko Department of Science and Technology, Sophia University, Assistant Professor, 理工学部, 助手 (80245795)
SORIMACHI Hiroyuki Institute of Molecular and Cellular Biosciences, The University of Tokyo, Assist, 分子細胞生物学研究所, 助手 (10211327)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Dystrophy / Dystrophin / treatment |
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| Research Abstract |
Dystrophin is a 420kD cytoskeletal protein and is defective in X-linked Duchenne muscular dystrophy. Polyclonal antibody against the C-terminal domain of dystrophin reacted with a 420kD dystrophin-related protein (DRP), which maps to chromosome 6 in human as well as in mouse. Overexpression of DRP was seen in dystrophin-deficient mdx muscles. These results were confirmed by using a specific antibody raised against predicted amino acid sequences of DRP.
We investigated the developmental regulation of DRP expression in control mouse muscles. DRP is highly expressed in embryos and gradually decreased thereafter. In contrast to DRP, dystrophin is not demonstrated in fetal muscles, but rather appeared at 2 days after birth, after which a significant increase in content was observed. This reciprocal expression of DRP and dystrophin suggests that DRP is an isoform of dystrophin in fetal skeletal muscle.
DRP has a similar molecular mass and localization as dystrophin, but is solubilized differently after detergent treatment. Therefore, there should be minor but distinct differences in physicochemical properties of DRP and dystrophin. Overexpression of DRP in dystrophic muscles may prevent or retard the onset of the disease.
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Report
(3 results)
Research Products
(17 results)
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[Publications] Takemitsu, M., Ishiura, S., Koga, R., Kamakura, K., Arahata, K., Nonaka, I.and Sugita, H.: "The localization of dystrophin-related protein in the mouse skeletal muscle." Biochem.Biophys.Res.Commun.180. 1179-1186 (1991)
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[Publications] Arikawa, E., Arahata, K., Ishiura, S., Nonaka, I.and Sugita, H.: "Immunocytochemical analysis of dystrophin in muscular dystrophy. In Duchenne Muscular Dystrophy (Kakulas, B.A.et al, eds.) Raven" In Duchenne Muscular Dystrophy (Kakulas, B.A.et al.eds.) Raven Press, New York. 81-88 (1992)
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[Publications] Koga, R., Ishiura, S., Arahata, K., Takakuwa, T., Nonaka, I.and Sugita, H.: "Quantitative analysis of dystrophin in human and rodent muscles." Biomed.Res.13. 215-219 (1992)
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[Publications] Koga, R., Ishiura, S., Takemitsu, M., Kamakura, K., Matsuzaki, T., Arahata, K., Nonaka, I.and Sugita, H.: "Immunoblot analysis of dystrophin-related protein." Biochim.Biophys.Acta. 1180. 257-261 (1993)
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[Publications] Sorimachi, H., Toyama-Sorimachi, N., Saido, T.C., Kawasaki, H., Sugita, H., Miyasaka, M., Arahata, K., Ishiura, S.and Suzuki, K.: "Muscle specific calpain, p94, is degraded by autolysis immediately after translation, resulting in disappearance from muscle." J.Biol.Chem.268. 10593-10605 (1993)
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