A CK19CreERT knockin mouse line allows for conditional DNA recombination in epithelial cells in multiple endodermal organs
A CK19CreERT knockin mouse line allows for conditional DNA recombination in epithelial cells in multiple endodermal organs
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DOI：
10.1002/dvg.20397
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发表时间：
2008-06-01
期刊：
影响因子：
1.5
通讯作者：
Gu, Guoqiang
中科院分区：
文献类型：
--
作者：
Means, Anna L.;Xu, Yanwen;Gu, Guoqiang
Cre/ loxp介导的DNA重组允许在胚胎发育和组织再生过程中进行基因功能和细胞谱系分析。在这里，我们描述了K19（CreERT）小鼠系的推导，其中他莫昔芬可激活的CreER(T)被敲入内源性细胞角蛋白19位点。在没有他莫昔芬的情况下，仅在不到1%的胃和肠上皮细胞中检测到漏漏的Cre活性，而在胰腺和肝上皮组织中则没有。在出生后给药的动物中，他莫昔芬以剂量依赖的方式诱导胰管、肝管、胃和肠上皮细胞广泛的DNA重组。值得注意的是，我们发现Cre活性可以在假定的肠道干细胞/祖细胞中被诱导，这些细胞可以长期维持Cre报告基因的肠道上皮表达。因此，该小鼠系将为在正常组织稳态和再生过程中操纵基因活性和多器官细胞谱系标记提供有价值的试剂。
Cre/LoxP-mediated DNA recombination allows for gene function and cell lineage analyses during embryonic development and tissue regeneration. Here, we describe the derivation of a K19(CreERT) mouse line in which the tamoxifen-activable CreER(T) was knocked into the endogenous cytokeratin 19 locus. In the absence of tamoxifen, leaky Cre activity could be detected only in less than 1% of stomach and intestinal epithelial cells, but not in pancreatic or hepatic epithelial tissues. Tamoxifen administration in postnatal animals induced widespread DNA recombination in epithelial cells of pancreatic ducts, hepatic ducts, stomach, and intestine in a dose-dependent manner. Significantly, we found that Cre activity could be induced in the putative gut stem/progenitor cells that sustained long-term gut epithelial expression of a Cre reporter. This mouse line should therefore provide a valuable reagent for manipulating gene activity and for cell lineage marking in multiorgans during normal tissue homeostaisis and regeneration.