| Budget Amount *help |
¥3,650,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
In a mito-mouse, which has 4698bp deletion mutation of mitochondrial (mt) DNA, dies from renal failure complicating with focal glomerular sclerosis (FGS) lesion, responding to increasing amount of mutation rate of mtDNA. We try to analyze mechanisms for developing FGS lesion in mito-mouse in this study.
In mito-mouse, proteinuria was detected in a mouse with the mutatied mtDNA exceeding 70% at the age of 18 weeks, which came to the peak at the age of 20weeks, then finally died at the age of 22weeks. Proteinuria was also detected in a mouse with the mutation rate between 50-69% at the age of 20weeks, although it could live until 28weeks while proteinuria gradually had increased. In the case of a mouse with the mutation rate between 10-49%, proteinuria was slightly observed at the age of 28weeks. A mouse with the mutation rate exceeding 70% revealed FGS lesions after the age of 20weeks, which developed global sclerosis at high rate afterwards. The expression levels of both intraglomerular nephrin and podocin increased when proteinuria level came to the peak point. The mRNA of both proteins was observed after the peak of proteinuria, nevertheless, the production of proteins, as well as that of mRNA, both dropped down afterwards.
From our study, accumulation of abnormal mtDNA in glomerular epithelium results in up-regulation of slit membrane protein and mRNA during nephritic phase, however, with ageing and more accumulated abnormal mtDNA results in detachment of glomerular epithelium from GBM and forms FGS lesion.
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