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利用条件性转基因技术研究肠道稳态与肿瘤形成。

Intestinal homeostasis and neoplasia studied using conditional transgenesis.

作者信息

Marsh Victoria, Clarke Alan

机构信息

Cardiff University, Cardiff School of Biosciences, Cardiff, UK.

出版信息

Expert Rev Anticancer Ther. 2007 Apr;7(4):519-31. doi: 10.1586/14737140.7.4.519.

DOI:10.1586/14737140.7.4.519
PMID:17428172
Abstract

Constitutive mouse models of intestinal neoplasia, such as the Apc(min/+) (multiple intestinal neoplasia) mouse have proven valuable tools both for furthering our understanding of tumorigenesis and for the development of therapeutic strategies. However, the in vivo study of a number of genes has been precluded by their absolute requirement during embryonic development. This has led to the development of conditional strategies that allow gene regulation in vivo. This review describes the principal techniques used to achieve conditional transgenesis within the mouse intestine, with a particular focus upon the Cre-Lox and Tet-regulable systems. Further, we discuss how these techniques are being used to dissect the mechanisms governing both normal homeostasis and neoplastic development within the intestine.

摘要

肠道肿瘤形成的组成型小鼠模型,如Apc(min/+)(多发性肠道肿瘤)小鼠,已被证明是推进我们对肿瘤发生的理解以及开发治疗策略的宝贵工具。然而,由于许多基因在胚胎发育过程中的绝对需求,对它们的体内研究受到了限制。这导致了允许体内基因调控的条件策略的发展。本综述描述了在小鼠肠道内实现条件转基因的主要技术,特别关注Cre-Lox和Tet可调控系统。此外,我们讨论了这些技术如何被用于剖析肠道内正常稳态和肿瘤发生的调控机制。

相似文献

1
Intestinal homeostasis and neoplasia studied using conditional transgenesis.利用条件性转基因技术研究肠道稳态与肿瘤形成。
Expert Rev Anticancer Ther. 2007 Apr;7(4):519-31. doi: 10.1586/14737140.7.4.519.
2
Mutated K-ras(Asp12) promotes tumourigenesis in Apc(Min) mice more in the large than the small intestines, with synergistic effects between K-ras and Wnt pathways.突变型K-ras(Asp12)在Apc(Min)小鼠中促进肿瘤发生的作用在大肠比小肠更明显,且K-ras和Wnt信号通路之间存在协同效应。
Int J Exp Pathol. 2009 Oct;90(5):558-74. doi: 10.1111/j.1365-2613.2009.00667.x.
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Cooperation between the thyroid hormone receptor TRalpha1 and the WNT pathway in the induction of intestinal tumorigenesis.甲状腺激素受体 TRα1 与 WNT 通路在诱导肠道肿瘤发生中的合作。
Gastroenterology. 2010 May;138(5):1863-74. doi: 10.1053/j.gastro.2010.01.041. Epub 2010 Jan 28.
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A targeted constitutive mutation in the APC tumor suppressor gene underlies mammary but not intestinal tumorigenesis.APC肿瘤抑制基因中的靶向组成性突变是乳腺肿瘤发生的基础,但不是肠道肿瘤发生的基础。
PLoS Genet. 2009 Jul;5(7):e1000547. doi: 10.1371/journal.pgen.1000547. Epub 2009 Jul 3.
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Fishing for intestinal cancer models: unraveling gastrointestinal homeostasis and tumorigenesis in zebrafish.捕捞肠道癌模型:揭示斑马鱼胃肠道稳态和肿瘤发生的机制。
Zebrafish. 2009 Dec;6(4):361-76. doi: 10.1089/zeb.2009.0617.
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Stromal Indian hedgehog signaling is required for intestinal adenoma formation in mice.基质 Indian hedgehog 信号对于小鼠肠道腺瘤的形成是必需的。
Gastroenterology. 2015 Jan;148(1):170-180.e6. doi: 10.1053/j.gastro.2014.10.006. Epub 2014 Oct 13.
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Interaction of Muc2 and Apc on Wnt signaling and in intestinal tumorigenesis: potential role of chronic inflammation.Muc2与Apc在Wnt信号通路及肠道肿瘤发生中的相互作用:慢性炎症的潜在作用
Cancer Res. 2008 Sep 15;68(18):7313-22. doi: 10.1158/0008-5472.CAN-08-0598.
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Intestinal epithelial-specific PTEN inactivation results in tumor formation.肠道上皮细胞特异性 PTEN 失活导致肿瘤形成。
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A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine.p53在调节肠道中Apc缺失的直接表型方面作用有限。
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Tensin4 (TNS4) is upregulated by Wnt signalling in adenomas in multiple intestinal neoplasia (Min) mice.张力蛋白4(TNS4)在多发性肠道肿瘤(Min)小鼠的腺瘤中通过Wnt信号上调。
Int J Exp Pathol. 2020 Jun;101(3-4):80-86. doi: 10.1111/iep.12352. Epub 2020 Jun 22.

引用本文的文献

1
Intestinal stem cells lacking the Math1 tumour suppressor are refractory to Notch inhibitors.缺乏 Math1 肿瘤抑制因子的肠干细胞对 Notch 抑制剂有抗性。
Nat Commun. 2010 May 17;1(2):18. doi: 10.1038/ncomms1017.