| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Research Abstract |
A missense mutation in crystallin, alpha B(CryAB) causes desmin-related cardiomyopathy, which is characterized by the formation of aggresomes containing CryAB. Cardiac disease in desmin-related cardiomyopathy can be recapitulated in transgenic(TG) mice by expressing the mutant CryAB protein specifically in the cardiomyocytes, which causes perinuclear formation of aggresomes. To analyze the role of HDAC6 in cardiac disease in desmin-related cardiomyopathy, cardiac-specific TG mice with overexpressed dominant negative HDAC6 or wild-type HDAC6 were generated. The mice with dominant negative HDAC6 showed increased acetylated tubulin levels concomitantly with higher numbers of CryAB-positive aggresomes and enhancement of heart weight/body weight ratio, while overexpression of wild-type HDAC6 was protective in the mutant CryAB TG mice hearts. These results indicate that HDAC6 inhibition exacerbates cardiac disease in mice with desmin-related cardiomyopathy.
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