Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice
Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice
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DOI：
10.1023/a:1013063514007
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发表时间：
2001-12-01
影响因子：
3
通讯作者：
Hennighausen, L
中科院分区：
文献类型：
--
作者：
Wagner, KU;McAllister, K;Hennighausen, L
基于Cre-loxP的基因缺失方法有望增强我们对控制乳腺发育和乳腺癌的分子途径的理解。我们早些时候报道了在小鼠乳腺肿瘤病毒(MMTV)长末端重复序列(LTR)的控制下，表达Cre重组酶的转基因小鼠的产生。这些小鼠已经成为一种有价值的研究工具，可以删除特定于乳腺、其他分泌器官和雌性生殖系的基因。我们现在已经用rosa26-lox-Stop-lox-LacZ报告菌株深入表征了MMTV-Cre转基因的表达，以确定Cre在单细胞水平上的时空激活。我们的结果表明，MMTV介导的Cre激活仅限于不同分泌组织和造血系统的特定细胞类型。其次，Cre表达的时间因组织和细胞类型的不同而不同。一些组织在胚胎发育过程中表达Cre，而另一些选定的细胞类型在青春期前后高度激活Cre，这表明类固醇激素对MMTV-LTR的转录激活有很强的影响。第三，Cre在雌性生殖系中的表达仅限于单个小鼠品系，因此依赖于转基因整合的位置。这项研究提供的信息将指导研究人员研究相关基因缺失时可能出现表型的细胞类型和发育阶段。
Cre-loxP based gene deletion approaches hold great promise to enhance our understanding of molecular pathways controlling mammary development and breast cancer. We reported earlier the generation of transgenic mice that express the Cre recombinase under the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). These mice have become a valuable research tool to delete genes specifically in the mammary gland, other secretory organs, and the female germline. We have now characterized in depth the expression of the MMTV-Cre transgene using the ROSA26-lox-Stop-lox-LacZ reporter strain to determine the temporal and spatial activation of Cre on the level of single cells. Our results show that MMTV-mediated Cre-activation is restricted to specific cell types of various secretory tissues and the hematopoietic system. Secondly, the timing of Cre expression varies between tissues and cell types. Some tissues express Cre during embryonic development, while other selected cell types highly activate Cre around puberty, suggesting a strong influence of steroid hormones on the transcriptional activation of the MMTV-LTR. Thirdly, Cre expression in the female germline is restricted to individual mouse lines and is therefore dependent on the site of integration of the transgene. Information provided by this study will guide the researcher to those cell types and developmental stages at which a phenotype can be expected upon deletion of relevant genes.