Functional analyses of ATF-2 gene family members by using knockout-mouse

使用敲除小鼠对 ATF-2 基因家族成员进行功能分析

• 批准号: 12670126
• 负责人: MAEKAWA Toshio
• 金额: $ 2.11万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670126/
• 关键词: Transcription factor; ATF-2; Mammary tumour; GADD45; APC; c-jun; Anisomycin; Knockoutmouse; ATF2

We have generated and anaiyzed the mutant mouse lacking transcription factor ATF-2 gene far members.1.ATF-2 heterozygously knockout female mouse developed mammary tumours at very high ratio 18/ : Most of these tumours were adenocarcinoma scirrhus.2, By using Tip-Technology, we have found that the expressions of APC and c-jun are reduced sev folds in ATF-2 deficient MEF.3, We have found that the induction of GADD45 gene by anisomycin is inhibited in the ATF-2 defic cell line.4, The expression levels of GADD45 gene were much reduced in the tumours than in normal mammal5, ATF-2 homozygously and heterozygously knockout MEFs that express activated RAS develo tumours in nude-mouse at 100%, but wild type MEF that express activated RAS couldn't develop tumours.6, From these results we can say that ATF-2 heterozygously knockout femaie mouse have high potent to develop tumours.

我们已经产生并分析了转录因子ATF-2基因far成员缺失的突变小鼠。1. ATF-2基因异源敲除的雌性小鼠发生乳腺肿瘤的比率非常高，为18/：2、利用Tip-Technology技术，我们发现在ATF-2缺陷的MEF中APC和c-jun的表达降低了数倍。我们发现，在ATF-2缺陷细胞系中，茴香霉素对GADD 45基因的诱导受到抑制。4、GADD 45基因在肿瘤中的表达水平比正常哺乳动物中低得多。5、ATF-2同源和异源敲除的MEFs表达激活的RAS。而表达激活RAS的野生型MEF不发生肿瘤。6、从这些结果可以看出ATF-2异源敲除雌性小鼠具有高的发生肿瘤的潜能。

项目成果

Tanaka Y, Naruse I, Hongo T, Xu M, Nakahata T, Maekawa T. Ishii S: "Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREB-binding protein"Mech Dev.. 95. 133-145 (2000)

Tanaka Y、Naruse I、Hongo T、Xu M、Nakahata T、Maekawa T. Ishii S：“CREB ​​结合蛋白的小鼠无效突变体中的广泛脑出血和胚胎致死”Mech Dev.. 95. 133-145 (2000

Tanaka Y,Naruse I,Hongo T,Xu M,Nakahata T,Maekawa T,Ishii S.: "Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREB-binding protein."Mech Dev.. 95. 133-45 (2000)

Tanaka Y、Naruse I、Hongo T、Xu M、Nakahata T、Maekawa T、Ishii S.：“CREB ​​结合蛋白的小鼠无效突变体导致广泛脑出血和胚胎致死。”Mech Dev.. 95. 133-45

TanakaY, Naruse I, Hongo T, Xu M, Nakahata T. Maekawa T. Ishil S: "Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREBbinding protein."Mech Dev. 95. 133-145 (2000)

TanakaY、Naruse I、Hongo T、Xu M、Nakahata T. Maekawa T. Ishil S：“CREB ​​结合蛋白的小鼠无效突变体导致广泛的脑出血和胚胎致死。”Mech Dev。

Shinagawa T, Dong HD, Xu M, Maekawa T, Ishii S: "The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice."EMBO J.. 15. 2280-2291 (2000)

Shinakawa T、Dong HD、Xu M、Maekawa T、Ishii S：“编码组蛋白脱乙酰酶复合物成分的 sno 基因在小鼠中充当肿瘤抑制因子。”EMBO J.. 15. 2280-2291 (2000

Shinagawa T, Dong HD, Xu M, Maekawa T, Ishii S: "The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice"EMBO J.. 15. 2280-2291 (2000)

Shinakawa T、Dong HD、Xu M、Maekawa T、Ishii S：“编码组蛋白脱乙酰酶复合物成分的 sno 基因在小鼠中充当肿瘤抑制因子”EMBO J.. 15. 2280-2291 (2000)