Leaf Irina, Tennessen Jason, Mukhopadhyay Mahua, Westphal Heiner, Shawlot William
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
Genesis. 2006 Dec;44(12):573-8. doi: 10.1002/dvg.20248.
Secreted frizzled related protein (Sfrp) genes encode extracellular factors that can modulate Wnt signaling. During early post-implantation mouse development Sfrp5 is expressed in the anterior visceral endoderm (AVE) and the ventral foregut endoderm. The AVE is important in anterior-posterior axis formation and the ventral foregut endoderm contributes to multiple gut tissues. Here to determine the essential role of Sfrp5 in early mouse development we generated Sfrp5-deficient mice by gene targeting. We report that Sfrp5-deficient mice are viable and fertile. To determine whether the absence of an axis phenotype might be due to genetic redundancy with Dkk1 in the AVE we generated Sfrp5;Dkk1 double mutant mice. AVE development and primitive streak formation appeared normal in Sfrp5(-/-);Dkk1(-/-) embryos. These results indicate that Sfrp5 is not essential for axis formation or foregut morphogenesis in the mouse and also imply that Sfrp5 and Dkk1 together are not essential for AVE development.
分泌型卷曲相关蛋白（Sfrp）基因编码能够调节Wnt信号传导的细胞外因子。在小鼠植入后早期发育过程中，Sfrp5在前肠内胚层（AVE）和腹侧前肠内胚层中表达。AVE在前后轴形成中起重要作用，腹侧前肠内胚层则参与多种肠道组织的形成。在此，为了确定Sfrp5在小鼠早期发育中的关键作用，我们通过基因靶向技术构建了Sfrp5基因缺失小鼠。我们发现Sfrp5基因缺失小鼠能够存活且可育。为了确定轴表型的缺失是否可能是由于AVE中Sfrp5与Dkk1存在基因冗余，我们构建了Sfrp5;Dkk1双突变小鼠。在Sfrp5(-/-);Dkk1(-/-)胚胎中，AVE发育和原条形成看起来正常。这些结果表明，Sfrp5对小鼠的轴形成或前肠形态发生并非必不可少，并暗示Sfrp5和Dkk1共同作用对AVE发育也并非必不可少。
