| Project/Area Number |
08457224
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kumamoto University |
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Principal Investigator |
MIIKEA Teruhisa Kumamoto University School of Medicine, Department of Child Development, Professor, 医学部, 教授 (90040617)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Masakatsu Kumamoto University School of Medicine, Department of Child Development,, 医学部・附属病院, 医員
KIMURA Shigemi Kumamoto University School of Medicine, Department of Child Development,, 医学部・附属病院, 助手 (60284767)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | dystrophin / promoter / gene therapy / transgenic mouse / lacZ / regulatory region / 発現制御機構 / 標的遺伝子組み換え / 発現調節制御機構 |
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| Research Abstract |
We have been trying to know the physiological function of dystrophin (dy) to develop effective clinical and gene therapy, during last 10 years. We considered that investigation of regulatory region of dy expression is reasonable way to know the physiological function of dy. Because of this view point we analyzed muscle type dy promoter region, using trausgenic mice. We reported a 0.9kb fragment from a mouse dy muscle promoter that contains the regulatory elements required for expression of dy only in the right heart. In this study, to further characterize the regulation of muscle type promoter, we analyzed promoter activity and tissue specificity using a total 14kb fragment around the human dy muscular-specific exon 1 in vitro and in vivo. Lu vitro analysis showed that the lacZ construct of the 7kb promoter and 7kb intron 1 was expressed 2.5 times as strongly as the lacZ construct of only the 7kb promoter in C2/4 myotubes. In vivo analysis revealed expression of both constructs in the whole heart, skeletal muscle and vascular smooth muscle in embryos. However, in adults, the expression in skeletal muscle disappeared. The results showed that the 7kb upstream region and the 7kb intronic region included responsible elements for the expression in the heart, but not in skeletal muscle in vivo. In future investigation we have to consider and pay attention to the dy localization on the smooth muscle of the vascular system, to show correct way to go for the clinical and gene therapy.
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