| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
This study is aimed to determine if hsp60 dysfunction leads to cardiomyopathy. We have developed a zebrafish mutant, nbl, which has a missense mutation in hsp60, leading to the loss of function.WT embryos showed higher survival rate (81%), compared to 65% in case of nbl homozygous mutant, when subjected to 33°C. Surprisingly, 92% of nbl mutants showed a pericardial edema. Also, nbl homozygous mutants showed the sudden death around 8 months post fertilization (mpf). In 8 mpf, nbl mutants showed dilated heart and high ROS expression. mRNA expression pattern of atg5, atg3 and gabarap were found to very high in nbl homozygous compared to WT. Further, analysis of genetically unrelated patients with familial DCM, who had no mutations in the known DCM-causing genes, identified an hsp60 mutation in one DCM family in which two of four mutation prone individuals died suddenly. Over expression of nbl type or DCM patient-type mutation in Hsp60 increases autophagosomes.
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