| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
We investigated the role of APJ ligand ELABELA and novel heart failure gene candidates in controlling heart functions by utilizing CRISPR/Cas9 genome editing in ES cells and functional analyses of G0 mice. ELA peptide treatment improved heart function and hypertrophy and reduced cardiac fibrosis in mice with TAC pressure overload. Mechanistically, ELA down-regulated transcription of ACE and thereby negatively regulates renin-angiotensin system. We also generated several new lines of mutant G0 mice for heart failure gene candidates and analyzed heart functions. Furthermore, we crossed the G0 mice for F1 and F2 generations and analyzed heart functions, leading to confirmation of 5 heart failure genes. The candidate approach with rapid generation and functional screening is efficient and useful in identifying novel heart failure genes and might contribute to boosting up cardiovascular research.
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