| Budget Amount *help |
¥62,660,000 (Direct Cost: ¥48,200,000、Indirect Cost: ¥14,460,000)
Fiscal Year 2014: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2013: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2012: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2011: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2010: ¥21,710,000 (Direct Cost: ¥16,700,000、Indirect Cost: ¥5,010,000)
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| Outline of Final Research Achievements |
Recent genome-wide association studies have demonstrated an association between MYH6, the gene encoding α-myosin heavy chain (α-MHC), and sinus node function in the general population. We identified an in-frame 3-bp deletion predicted to delete one residue (delE933) at the highly conserved coiled-coil structure within the binding motif to myosin-binding protein C (MyBP-C) in one patient. Co-immunoprecipitation analysis revealed sarcomere impairments. The HL-1 stably expressing delE933 showed slower conduction velocity on than wild-type. Furthermore, targeted knock-down of MYH6 in zebrafish significantly reduced the heart rate, which was rescued by co-expressed wild-typeα-MHC but not by delE933. The novel MYH6 mutation delE933 causes both structural damage of the sarcomere and functional impairments on atrial action propagation. This report reinforces the relevance of MYH6 for sinus node function and identifies a novel pathophysiology underlying familial SSS
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