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Mig-6条件性无效等位基因的产生。

Generation of a Mig-6 conditional null allele.

作者信息

Jin Nili, Gilbert Jennifer L, Broaddus Russell R, Demayo Francesco J, Jeong Jae-Wook

机构信息

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

出版信息

Genesis. 2007 Nov;45(11):716-21. doi: 10.1002/dvg.20348.

DOI:10.1002/dvg.20348
PMID:17987665
Abstract

Mitogen-inducible gene 6 (Mig-6) is a stress-induced gene that serves as a negative regulator of epidermal growth factor (EGF) signaling and acts as a tumor suppressor. Ablation of Mig-6 results in a significant percentage of embryo lethality as well as abnormalities in multiple tissues. To understand the physiological roles of Mig-6, a conditional null allele, Mig-6(f/f) was generated by introducing LoxP sites that flank exons 2 and 4. The Mig-6(f/f) allele was validated by generating recombined Mig-6(-/-) mice using the Zp3-Cre system. The conditional null allele was confirmed by assaying for Mig-6 gene expression in liver, lung, uterus, and skin. The recombined Mig-6(-/-) mice developed pathological changes, such as degenerative joint diseases and skin hyperplasia similar to the previously reported Mig-6 germline null allele. In addition, these mice also had enlarged uteri with endometrial hyperplasia. In summary, this Mig-6(f/f) mouse is a useful tool for the functional study of the Mig-6 gene in a tissue-specific fashion.

摘要

丝裂原诱导基因6(Mig-6)是一种应激诱导基因,作为表皮生长因子(EGF)信号通路的负调节因子,发挥肿瘤抑制作用。Mig-6基因缺失会导致相当比例的胚胎致死以及多种组织出现异常。为了解Mig-6的生理作用,通过在第2和第4外显子两侧引入LoxP位点,构建了条件性无效等位基因Mig-6(f/f)。利用Zp3-Cre系统产生重组的Mig-6(-/-)小鼠,验证了Mig-6(f/f)等位基因。通过检测肝脏、肺、子宫和皮肤中的Mig-6基因表达,证实了条件性无效等位基因。重组的Mig-6(-/-)小鼠出现了病理变化,如退行性关节疾病和皮肤增生,类似于先前报道的Mig-6种系无效等位基因。此外,这些小鼠还出现子宫增大和子宫内膜增生。总之,这种Mig-6(f/f)小鼠是一种以组织特异性方式对Mig-6基因进行功能研究的有用工具。

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Generation of a Mig-6 conditional null allele.Mig-6条件性无效等位基因的产生。
Genesis. 2007 Nov;45(11):716-21. doi: 10.1002/dvg.20348.
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Critical tumor suppressor function mediated by epithelial Mig-6 in endometrial cancer.上皮细胞 Mig-6 通过关键肿瘤抑制作用介导子宫内膜癌发生。
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Evidence that MIG-6 is a tumor-suppressor gene.MIG-6是一种肿瘤抑制基因的证据。
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Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease.Mig-6调节子宫类固醇激素反应性,并在子宫内膜疾病中表现出表达改变。
Proc Natl Acad Sci U S A. 2009 May 26;106(21):8677-82. doi: 10.1073/pnas.0903632106. Epub 2009 May 13.

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