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遺伝子改変マウスを用いた消化器癌発生進展におけるRASAL1の機能解析

使用转基因小鼠进行RASAL1在胃肠道癌症发生和进展中的功能分析

基本信息

批准号：
22590678
负责人：
杉本貴史
金额：
$ 2.08万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590678/
关键词：
消化器癌 RASシグナル遺伝子改変マウス RASGAP

项目摘要

RASAL1はRASの活性を負に制御するRASGAPであり、当科ではその発現低下によりRASが活性化された大腸癌、胃癌がかなりの頻度で存在することを示した。本研究ではRASAL1の消化器癌発生進展への関与のメカニズムを明らかにするため、RASAL1の組織特異的ノックアウトマウスを作製し、その表現型を解析することとした。まず、マウスRasal1のRasGAPドメインをコードするエクソン11から13までを条件的にノックアウトするマウス(Rasall flox)の樹立に成功した。現在Rasall floxマウスを全身でCreを発現するCAG-Creマウス、大腸特異的、膵特異的CreマウスであるCdx2-Cre,Ptfla-Creマウスと交配することにより、各組織特異的Rasal1ノックアウトマウスの作製を進めている。まだpreliminaryであるが全身でのRasal1ホモノックアウトが得られている。Cdx2-Cre;Rasal1^<flox/flox>マウスも得られており、今後表現型の解析を進める。また、Rasal1単独のノックアウトでは明らかな表現型が現れない場合でも、他の遺伝子改変マウスの表現型をRasal1ノックアウトが増強あるいは減弱させることも考えられるため、腸管にポリープを生じるAPCノックアウトマウスとの交配もすでに開始している。今後上記のマウスに加えて、b-catenin活性化型変異を条件的に発現するマウス(b-catenin(exon3)flox)やTGFbII型受容体の条件的ノックアウトマウス(TGFbR2flox)とも交配を進める予定である。

The activity of RASAL1 RAS in the control of RASGAP infection, the presence of low activity in the department, the activation of RAS, the severity of major cancer and gastric cancer. In this study, the patients with advanced RASAL1 digestive tract cancer and the patients with advanced digestive tract cancer were analyzed. The results showed that the patients with cancer of the digestive apparatus were not affected by the cancer of the digestive system, the patients with advanced cancer of the digestive system, the patients with cancer of the digestive tract, the patients with cancer of the digestive system, the patients with cancer of the digestive apparatus, the patients with cancer of the digestive apparatus, the patients with cancer of the digestive apparatus, the patients with cancer of the digestive apparatus, the patients with cancer of the digestive apparatus, the patients with cancer of the digestive apparatus, the patients with cancer of the digestive apparatus, the patients with cancer of the digestive apparatus, the patients with cancer of the digestive apparatus, the patients with cancer of the digestive system, the patients with advanced digestive tract cancer, the patients with advanced digestive tract cancer, the patients with advanced digestive tract cancer, the patients with advanced digestive tract cancer and the patients with advanced digestive tract cancer. Rasal1, RasGAP, Rasall flox, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, 13, 11, Now in Rasall flox, all over the body, there are CAG-Cre genes, special Cre genes, special Cdx2-Cre,Ptfla-Cre genes, mating genes, and the special Rasal1 genes of each organization. Preliminary the whole body, Rasal1 the whole body, get the crap out of you. Cdx2-Cre; Rasal1 ^ & lt;flox/flox> system has been improved, and the table model has been analyzed in the future. For example, if you want to know that you are not in the market, you will not be able to do so. In this case, you will not be able to do so. In this case, you will be able to improve the performance of your Rasal1. You will not be able to do so. You will not be able to do so. In the future, the conditions of b-catenin (exon3) flox (TGFbII) and TGFbII recipients (TGFbII) were determined by the method of mating (TGFbR2flox), which was used to determine the level of mating.