Department of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Kingsbury Drive, Bundoora, Victoria, Australia 3086.
Cell Death Dis. 2012 Aug 9;3(8):e365. doi: 10.1038/cddis.2012.110.
Use of the cre transgene in in vivo mouse models to delete a specific 'floxed' allele is a well-accepted method for studying the effects of spatially or temporarily regulated genes. During the course of our investigation into the effect of cyclic adenosine 3',5'-monophosphate-dependent protein kinase A (PKA) expression on cell death, we found that cre expression either in cultured cell lines or in transgenic mice results in global changes in PKA target phosphorylation. This consequently alters gene expression profile and changes in cytokine secretion such as IL-6. These effects are dependent on its recombinase activity and can be attributed to the upregulation of specific inhibitors of PKA (PKI). These results may explain the cytotoxicity often associated with cre expression in many transgenic animals and may also explain many of the phenotypes observed in the context of Cre-mediated gene deletion. Our results may therefore influence the interpretation of data generated using the conventional cre transgenic system.
在体内小鼠模型中使用 cre 转基因来删除特定的“floxed”等位基因是研究空间或时间调节基因影响的一种被广泛接受的方法。在我们研究环腺苷酸 3'，5'-单磷酸依赖性蛋白激酶 A（PKA）表达对细胞死亡的影响的过程中，我们发现 cre 在培养的细胞系或转基因小鼠中的表达导致 PKA 靶标磷酸化的全局变化。这进而改变基因表达谱，并改变细胞因子（如 IL-6）的分泌。这些效应依赖于其重组酶活性，并且可以归因于 PKA 的特定抑制剂（PKI）的上调。这些结果可能解释了在许多转基因动物中与 cre 表达相关的细胞毒性，并且也可以解释在 Cre 介导的基因缺失的背景下观察到的许多表型。因此，我们的结果可能会影响使用传统的 cre 转基因系统生成的数据的解释。
