Generation of Axin1 conditional mutant mice.
Generation of Axin1 conditional mutant mice.
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作者：
Xie, Rong;Jiang, Rulang;Chen, Di
Axin 1是经典Wnt信号通路的关键负调节因子。它是β-连环蛋白降解复合物中的浓度限制因子。Axin 1无效突变小鼠胚胎在胚胎第9.5天死亡，排除了使用这些突变小鼠对Axin 1在许多发育和生理过程中的作用进行直接遗传分析。在这项研究中，我们已经产生了小鼠携带两个直接重复loxP位点侧翼外显子2区的Axin 1基因。我们发现，携带Axin 1fx/fx等位基因的小鼠表现正常且具有生育能力。在Axin 1fx/fx小鼠与CMV-Cre转基因小鼠杂交后，通过Cre介导的体内切除有效地删除了编码N末端和G蛋白信号传导结构域的保守调控的loxP侧翼外显子2区域。此外，我们发现，Cre/loxP介导的Axin 1基因外显子2缺失的纯合子小鼠胚胎显示胚胎致死性和发育缺陷，与Axin 1 −/−小鼠报告的相似。因此，这种Axin 1fx/fx小鼠模型将是有价值的系统的组织特异性解剖的作用，Axin 1在胚胎和出生后的发展和疾病。
Axin1 is a critical negative regulator of the canonical Wnt-signaling pathway. It is a concentration-limiting factor in the β-catenin degradation complex. Axin1 null mutant mouse embryos died at embryonic day 9.5, precluding direct genetic analysis of the roles of Axin1 in many developmental and physiological processes using these mutant mice. In this study, we have generated mice carrying two directly repeated loxP sites flanking the exon 2 region of the Axin1 gene. We show that floxed-allele-carrying mice (Axin1fx/fx) mice appear normal and fertile. Upon crossing the Axin1fx/fx mice to the CMV-Cre transgenic mice, the loxP-flanked exon 2 region that encodes the N-terminus and the conserved regulation of G-protein signaling domain was efficiently deleted by Cre-mediated excision in vivo. Moreover, we show that mouse embryos homozygous for the Cre/loxP-mediated deletion of exon 2 of the Axin1 gene display embryonic lethality and developmental defects similar to those reported for Axin1−/− mice. Thus, this Axin1fx/fx mouse model will be valuable for systematic tissue-specific dissection of the roles of Axin1 in embryonic and postnatal development and diseases.
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