Generation of a mouse with conditionally activated signaling through the BMP receptor, ALK2
Generation of a mouse with conditionally activated signaling through the BMP receptor, ALK2
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DOI：
10.1002/dvg.20201
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发表时间：
2006-04-01
期刊：
影响因子：
1.5
通讯作者：
Mishina, Yuji
中科院分区：
文献类型：
--
作者：
Fukuda, Tomokazu;Scott, Gregory;Mishina, Yuji
BMP信号在各种组织中发挥多效性作用。以组织特异性方式过表达BMP信号传导的转基因小鼠品系将是有益的;然而，每个组织特异性转基因小鼠品系的生产是劳动密集型的。在这里，使用Cre-loxP系统，我们产生了通过I型受体ALK 2（或者称为AVCRI、ActRI或ActRIA）进行BMP信号传导的条件性过表达小鼠系。通过将该品系与Cre表达小鼠品系交配，Cre介导的重组去除了间插的floxed lacZ表达盒，从而允许由普遍存在的启动子CAG驱动的Alk 2（caAlk 2）的组成型活性形式的表达。Cre重组的组织特异性由Alk 2 cDNA后的双顺反子表达的EGFP监测。BMP信号的增加被证实SMAD 1/5/8在Cre重组发生的区域的异位磷酸化。这里描述的条件过表达系统提供了以组织特异性方式研究基因功能的多功能性，而不必产生独立的组织特异性转基因系。
BMP signaling plays pleiotropic roles in various tissues. Transgenic mouse lines that overexpress BMP signaling in a tissue-specific manner would be beneficial; however, production of each tissue-specific transgenic mouse line is labor-intensive. Here, using a Cre-loxP system, we generated a conditionally overexpressing mouse line for BMP signaling through the type I receptor ALK2 (alternatively known as AVCRI, ActRI, or ActRIA). By mating this line with Cre-expression mouse lines, Cre-mediated recombination removes an intervening floxed lacZ expression cassette and thereby permits the expression of a constitutively active form of Alk2 (caAlk2) driven by a ubiquitous promoter, CAG. Tissue specificity of Cre recombination was monitored by a bicistronically expressed EGFP following Alk2 cDNA. Increased BMP signaling was confirmed by ectopic phosphorylation of SMAD1/5/8 in the areas where Cre recombination had occurred. The conditional overexpression system described here provides versatility in investigating gene functions in a tissue-specific manner without having to generate independent tissue-specific transgenic lines.