| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Research Abstract |
Calreticulin(CRT) is a Ca2+-binding protein of the endoplasmic reticulum and essential for cardiac development. Cardiac-specific overexpression of calreticulin by α-myosin heavy chain promoter results in complete heart block and sudden death in transgenic mice. Here, to investigate further mechanism of calreticulin, we generate transgenic mice that cause temporal and spatial overexpression of calreticulin using cre-loxP system. The mice were cross-bred with Nkx2.5-Cre mice which express cre recombinase under control of Nkx2.5 promoter, a transcription factor essential for early cardiac development. Overexpression of calreticulin was associated with PR interval and QRS interval prolongation, bradycardia, sudden death between 6-week-old and 10-week-old. Furthermore, some of the NKx2.5-CRT transgenic mice revealed marked edema in 7-week-old. In conclusion, overexpression calreticulin in the heart is associated with a decrease in HCN1 expression and calreticulin plays an important role of HCN1 gene regulation.
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