Making conditional knockout mouse of the gene coding inversin and the significance of inversion in the cilia-dependent renal disease

反转蛋白基因条件性敲除小鼠的制作及其在纤毛依赖性肾病中的意义

• 批准号: 19590965
• 负责人: TSUCHIYA Ken
• 金额: $ 2.91万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19590965/
• 关键词: siRNA; 左右軸; ノックアウトマウス; 繊毛; 嚢胞腎; inv遺伝子; アデノウィルス; マイクロアレイ; 培養細胞

Vertebrate organisms have a common left-right asymmetry of their visceral organs. However, all unpaired organs of the chest and abdomen, such as heart, stomach, spleen and liver, develop from the midline in the fetus and localize to their normal positions in the adult. The phenotype of the inv mouse is a consistent mirror-image reversal of the left-right polarity (situs inversus) and cystic formation of the kidneys. In this study, the targeting vector of the inversion of embryonic turning (inv) for conditional knockout mounting interferon-induced promoter was constructed. Genomic southern hybridization indicated that these gene spans the whole deleted region, implying that the homozygous inv mice have intragenic deletion of this gene. We also analyzed the physiologic and pathophysiological findings of mice and renal tubular cells kidney associated with an inversion of embryonic turning. The results suggested that there might be a possibility that a cytoskeletal abnormality was involved in the mechanism and production of both structural abnormalities, inversion and cyst formation in the kidney.

脊椎动物的内脏器官有常见的左右不对称。然而，胸部和腹部的所有不成对的器官，如心脏、胃、脾和肝脏，都是从胎儿的中线发育起来的，并在成人时定位到正常的位置。INV小鼠的表型是左右两极(反位)一致的镜像颠倒和肾脏的囊状形成。本研究构建了条件性基因敲除干扰素诱导启动子的胚胎翻转倒置(INV)的靶向载体。基因组Southern杂交表明，这些基因跨越了整个缺失区，这意味着纯合子inv小鼠存在该基因的基因内缺失。我们还分析了与胚胎逆转相关的小鼠和肾小管细胞肾脏的生理学和病理生理学表现。结果提示，细胞骨架异常可能参与了肾脏结构异常、倒置和囊性形成的机制和产生。

项目成果

Protective effect of carbon monoxide donor compounds in endotoxin-induced acute renal failure.

一氧化碳供体化合物在内毒素诱导的急性肾衰竭中的保护作用。

• 发表时间: 2007
• 期刊: Am J Nephrol 27
• 作者: Shiohira S;Yoshida T;Sugiura H;Shirota S;Tsuchiya K;Akiba T;Nitta K
• 通讯作者: Nitta K

ATF3 protects against renal ischemia-reperfusion injury

• DOI: 10.1681/asn.2005111155
• 发表时间: 2008-02-01
• 期刊: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
• 影响因子: 13.6
• 作者: Yoshida, Takumi;Sugiura, Hidekazu;Nitta, Kosaku
• 通讯作者: Nitta, Kosaku

Suppression of mafA mRNA with siRNA prevents adipose cell differentiation in 3T3-L1 cells.

用 siRNA 抑制 mafA mRNA 可阻止 3T3-L1 细胞中的脂肪细胞分化。

• 发表时间: 2009
• 期刊: Int J Mol Med 23
• 作者: Tsuchiya M;Maeda A;Suzuki A;Yasuda K;Yoshida T;Nitta K;Tsuchiya K*
• 通讯作者: Tsuchiya K*

In vivo suppression of mafA mRNA with siRNA and analysis of the resulting alteration of the gene expression profile in mouse pancreas by the microarray method

用 siRNA 体内抑制 mafA mRNA，并通过微阵列方法分析小鼠胰腺中基因表达谱的变化

• 发表时间: 2007
• 期刊: Biochemical Biophysical Research Communications 356
• 作者: M. Tsuchiya;T. Yoshid;S. Taniguchi;K. Yasuda;A. Maeda;A. Hayashi;K. Tsuchiya;et. al.
• 通讯作者: et. al.

The effect of eicosapentaenoic acid on renal function and volume in patients with ADPKD

• DOI: 10.1093/ndt/gfn144
• 发表时间: 2008-09-01
• 期刊: NEPHROLOGY DIALYSIS TRANSPLANTATION
• 影响因子: 6.1
• 作者: Higashihara, Eiji;Nutahara, Kikuo;Hamazaki, Tomohito
• 通讯作者: Hamazaki, Tomohito