Uetzmann Lena, Burtscher Ingo, Lickert Heiko
Helmholtz Zentrum München, Institute of Stem Cell Research, Ingolstädter Landstrasse 1, Neuherberg, Germany.
Genesis. 2008 Oct;46(10):515-22. doi: 10.1002/dvg.20410.
Foxa2 is a forkhead transcription factor expressed in the node, notochord, floorplate, and definitive endoderm and is required in the foregut endoderm for the normal development of the endoderm-derived organs, such as the liver, lung and pancreas. To conditionally inactivate genes in these tissues and organs, we have targeted a Cre recombinase into Exon 1 of the Foxa2 gene. We show, upon crossing to the ROSA26 reporter mice, that Cre expression from the Foxa2(iCre) knock-in allele specifically activates beta-galactosidase expression in the node, notochord, floorplate, and endoderm. In addition, we detect Cre recombination activity in the endoderm-derived organs including lung, liver, pancreas, and gastrointestinal tract throughout development. These results demonstrate that the Foxa2(iCre) knock-in mice are a valuable tool to analyze gene function in endoderm progenitors and endoderm-derived organs. Moreover, the widespread beta-galactosidase reporter activity in the endoderm suggests that Foxa2 marks a progenitor cell population, which gives rise to the majority of cells in endoderm-derived organs.
Foxa2是一种叉头转录因子,在节点、脊索、底板和定形内胚层中表达,在前肠内胚层中,它是内胚层衍生器官(如肝脏、肺和胰腺)正常发育所必需的。为了在这些组织和器官中条件性地使基因失活,我们将一种Cre重组酶靶向到Foxa2基因的外显子1中。我们发现,与ROSA26报告基因小鼠杂交后,Foxa2(iCre)敲入等位基因的Cre表达特异性地激活了节点、脊索、底板和内胚层中的β-半乳糖苷酶表达。此外,我们在整个发育过程中在内胚层衍生器官(包括肺、肝脏、胰腺和胃肠道)中检测到了Cre重组活性。这些结果表明,Foxa2(iCre)敲入小鼠是分析内胚层祖细胞和内胚层衍生器官中基因功能的有价值工具。此外,内胚层中广泛的β-半乳糖苷酶报告基因活性表明,Foxa2标记了一个祖细胞群体,该群体产生了内胚层衍生器官中的大多数细胞。