| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Noriyuki Kyoto Prefectural University of Medicine, 医学研究科, 助手 (90381954)
SHIBA Dai Kyoto Prefectural University of Medicine, 医学研究科, 助手 (50360722)
IIJIMA Norio Kyoto Prefectural University of Medicine, 医学研究科, 助手 (00285248)
鳴瀬 善久 京都府立医科大学, 医学研究科, 助手 (00326216)
大橋 憲太郎 京都府立医科大学, 医学研究科, 助手 (50332953)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2004: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2003: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Research Abstract |
The inv mouse, which is caused by loss of inv gene, shows reversal of left-right asymmetry as well as renal cysts. Mechanism by which loss of inv gene causes reversal of left-right asymmetry is unknown. However, it may be possible that reversal of left-right asymmetry and development of renal cysts share the same mechanisms.
The inv/inv : ; Δ C-GFP mice was created by introduction of c-terminus deleted inv gene fused to GFP protein. The mice show normal left-right asymmetry but still develop renal cysts. To understand role of inv protein, we compared gene expression between normal and inv mice. Expression of 37000 genes was analyzed by DNA microarray between RNAs from 4 weeks-old normal and inv/inv : ; Δ C-GFP mice kidneys. 446 genes show 4 times higher expression in cystic kidney than that in normal kidney. 122 genes show reduced expression in cystic kidney compared to that in normal kidney. We selected 15 genes and performed semi-quantitative RT-PCR to verify the microarray results. A
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ll examined genes by semi-quantitative RT-PCR confirmed the microarray results, but not quantitatively. Expression pattern of up-regulated genes among 15 genes were further analyzed by comparing to expression at newborn kidney. We found that these genes can be classified into two groups. The first group is that expression at newborn kidney is higher than that at 4 weeks-old kidney of normal mouse. In inv/inv : ; Δ C-GFP mice, expression at 4 weeks-old kidney keeps high level. Genes belongs to this group include Copeb, Egr2, Isg20, c-myc, Sox4, Tgfb2, Tgfi, and Runx1. The second group is that in normal mouse kidney, expression level of newborn kidney shows unchanged that of 4-weeks old kidney. In this group, expression level in cystic kidney is elevated. This group includes Crap, Irak3, Nkd2, Slit3 and Socs3.
These results suggested that up-regulation of genes seen in cystic kidneys may be induced by two mechanisms ; one is persistent high expression, the other is high expression induced cyst formation. Less
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