Adhikary Sovana, Peukert Karen, Karsunky Holger, Beuger Vincent, Lutz Werner, Elsässer Hans-Peter, Möröy Tarik, Eilers Martin
Institute for Molecular Biology and Tumor Research. Institute for Cytobiology and Cytopathology, University of Marburg, 35033 Marburg, Germany.
Mol Cell Biol. 2003 Nov;23(21):7648-57. doi: 10.1128/MCB.23.21.7648-7657.2003.
Miz1 is a member of the POZ domain/zinc finger transcription factor family. In vivo, Miz1 forms a complex with the Myc oncoprotein and recruits Myc to core promoter elements. Myc represses transcription through Miz1 binding sites. We now show that the Miz1 gene is ubiquitously expressed during mouse embryogenesis. In order to elucidate the physiological function of Miz1, we have deleted the mouse Miz1 gene by homologous recombination. Miz1(+/-) mice are indistinguishable from wild-type animals; in contrast, Miz1(-/-) embryos are not viable. They are severely retarded in early embryonic development and do not undergo normal gastrulation. Expression of Goosecoid and Brachyury is detectable in Miz1(-/-) embryos, suggesting that Miz1 is not required for signal transduction by Nodal. Expression of p21Cip1, a target gene of Miz1 is unaltered; in contrast, expression of p57Kip2, another target gene of Miz1 is absent in Miz1(-/-) embryos. Miz1(-/-) embryos succumb to massive apoptosis of ectodermal cells around day 7.5 of embryonic development. Our results show that Miz1 is required for early embryonic development during gastrulation.
Miz1是POZ结构域/锌指转录因子家族的成员。在体内，Miz1与Myc癌蛋白形成复合物，并将Myc募集到核心启动子元件上。Myc通过Miz1结合位点抑制转录。我们现在表明，Miz1基因在小鼠胚胎发育过程中普遍表达。为了阐明Miz1的生理功能，我们通过同源重组删除了小鼠Miz1基因。Miz1(+/-)小鼠与野生型动物没有区别；相反，Miz1(-/-)胚胎无法存活。它们在早期胚胎发育中严重滞后，不能进行正常的原肠胚形成。在Miz1(-/-)胚胎中可检测到Goosecoid和Brachyury的表达，这表明Miz1不是Nodal信号转导所必需的。Miz1的靶基因p21Cip1的表达未改变；相反，Miz1的另一个靶基因p57Kip2在Miz1(-/-)胚胎中不表达。Miz1(-/-)胚胎在胚胎发育第7.5天左右死于外胚层细胞的大量凋亡。我们的结果表明，Miz1是原肠胚形成期间早期胚胎发育所必需的。
