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Involvement of inv-calmodulin pathway for left-right asymmetry formation

inv-钙调蛋白途径参与左右不对称形成

基本信息

批准号：
15370095
负责人：
YOKOYAMA Takahiko
金额：
$ 8.38万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15370095/
关键词：
cyst kidney microarray inv 繊毛 policystin 腎臓

项目摘要

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 … More 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

Inv小鼠是由inv基因缺失引起的，表现出左右不对称的逆转和肾囊肿。Inv基因缺失导致左右不对称逆转的机制尚不清楚。INV/inv：；ΔC-gfp小鼠是通过将c-末端缺失的inv基因融合到gfp蛋白中而获得的。小鼠表现出正常的左右不对称，但仍会出现肾囊肿。为了了解inv蛋白的作用，我们比较了正常和inv小鼠的基因表达。用基因芯片技术分析了4周龄正常和inv/inv：；ΔC-gfp小鼠肾脏组织中37000个基因的表达。446个基因在囊性肾组织中的表达水平是正常肾组织的4倍。122个基因在囊性肾组织中的表达低于正常肾组织。我们选择了15个基因并进行半定量RT-PCR来验证微阵列的结果。A…半定量RT-PCR检测更多的基因证实了微阵列结果，但不是定量的。通过与新生儿肾脏表达的比较，进一步分析了15个基因中上调基因的表达模式。我们发现，这些基因可以分为两类。第一组为新生小鼠肾脏表达高于4周龄正常小鼠肾脏。在inv/inv：；ΔC-gfp小鼠中，4周龄肾脏中仍有较高的表达。属于这一组的基因包括Copeb、Egr2、Isg20、c-myc、Sox4、Tgfb2、Tgfi和RUNX1。第二组为正常小鼠肾脏，新生小鼠肾脏的表达水平与4周龄小鼠肾脏无明显差异。在本组中，囊性肾组织中的表达水平升高。这一组包括CRARP、IRAK3、NKD2、SLIT3和SOCS3。这些结果表明，在囊性肾脏中发现的基因上调可能由两种机制诱导：一种是持续高表达，另一种是高表达诱导囊变形成。较少