| Project/Area Number |
21500397
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
ARAI Yuji 独立行政法人国立循環器病研究センター, 分子生物学部, 室長 (30202724)
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| Project Period (FY) |
2009 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 遺伝子改変 / Nkx2-5 / 疾患モデル動物 |
|---|
| Research Abstract |
Human mutation in Nkx2-5, a cardiac homeobox gene, predominantly function in a dominant-negative fashion and cause a diverse set of congenital heart malformations that include septal defects, cardiomyopathy, outflow tract defects, hypoplastic left heart, and associated arrhythmias. Mice that harbor a complete global knockout of Nkx2-5 display early embryonic lethality and defects in cardiac looping morphogenesis, consistent with a role for Nkx2-5 in the early stages of cardiogenesis. To delineate the molecular mechanisms that link the loss of Nkx2-5 with cardiac disease phenotypes observed in human, we have produced Cre-recombinase-mediated deletion mice, Nkx2-5 floxed allele mice, that escape the early, complete lethality found in the global knockout mice. Nkx2-5 floxed allele mice were crossed with the heart-specific cre recombinase transgenic lines such as myosin light chain-2v cre andαmyosin heavy chain cre. Mice with heart-restricted knockout of Nkx2-5 display no structural effects but have progressive complete heart block and heart enlargement found in some patients with Nkx2-5 mutations. In these mice, the reduction of Nkx2-5 expression level results in hypoplasia of the conduction system and enlargement of heart.
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