2013 Fiscal Year Final Research Report
Modeling Duchenne muscular dystrophy using patient-derived iPS cells
| Project/Area Number |
24790383
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
MATSUO Masafumi 神戸学院大学, 大学院総合リハビリテーション学部, 教授 (10157266)
AWAYA Tomonari 京都大学, 大学院医学研究科発達小児科学, 助教 (20589593)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | iPS細胞 / 疾患再現 / 筋ジストロフィー |
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| Research Abstract |
In this study, we demonstrated the early pathogenesis of Duchenne muscular dystrophy (DMD) using patient-derived iPS cells. DMD-muscles differentiated from DMD-iPSCs exhibited similar gene expression profile and similar maturity as control iPSC-derived muscles, and no differentiation delay was observed in DMD-muscles. When DMD-muscles were exposed to electric stimulation, higher intracellular Ca2+ influx was observed in DMD-muscles than control-muscles. Larger cell damage was observed in DMD-muscles than control-muscles through overloading Ca2+ by ionomycin. Since these phenotype could be ameliorated by restored dystrophin expression by exon skip technics, we conclude that excessive Ca2+ influx is the trigger for the early pathogenesis of DMD caused by absence of dystrophin. According to our findings, we are going to develop new drugs targeting excessive Ca2+ influx by analyzing the mechanism which is caused by absence of dystrophin.
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