PDF(Pubmed)
Abstract：
IRF6 is a key genetic determinant of syndromic and non-syndromic cleft lip and palate. The ability to interrogate post-embryonic requirements of Irf6 has been hindered, as global Irf6 ablation in the mouse causes neonatal lethality. Prior work analyzing Irf6 in mouse models defined its role in the embryonic surface epithelium and periderm where it is required to regulate cell proliferation and differentiation. Several reports have also described Irf6 gene expression in other cell types, such as muscle, and neuroectoderm. However, analysis of a functional role in non-epithelial cell lineages has been incomplete due to the severity and lethality of the Irf6 knockout model and the paucity of work with a conditional Irf6 allele. Here we describe the generation and characterization of a new Irf6 floxed mouse model and analysis of Irf6 ablation in periderm and neural crest lineages. This work found that loss of Irf6 in periderm recapitulates a mild Irf6 null phenotype, suggesting that Irf6-mediated signaling in periderm plays a crucial role in regulating embryonic development. Further, conditional ablation of Irf6 in neural crest cells resulted in an anterior neural tube defect of variable penetrance. The generation of this conditional Irf6 allele allows for new insights into craniofacial development and new exploration into the post-natal role of Irf6.
摘要：
IRF6是综合征性和非综合征性唇腭裂的关键遗传决定因素。询问Irf6胚胎后需求的能力受到了阻碍，因为小鼠的整体Irf6消融会导致新生儿死亡。在小鼠模型中分析Irf6的先前工作定义了其在胚胎表面上皮和外胚层中的作用，在那里它是调节细胞增殖和分化所必需的。一些报道还描述了Irf6基因在其他细胞类型中的表达，比如肌肉，和神经外胚层.然而,由于Irf6基因敲除模型的严重程度和致死率以及对条件Irf6等位基因的缺乏工作，对非上皮细胞谱系中的功能作用的分析一直不完整。在这里，我们描述了一种新的Irf6浮动小鼠模型的产生和表征，以及在周皮和神经c谱系中Irf6消融的分析。这项工作发现，周皮中Irf6的丢失概括了轻度的Irf6无效表型，提示周胚层中Irf6介导的信号传导在调节胚胎发育中起着至关重要的作用。Further,有条件地消融神经c细胞中的Irf6导致可变外显率的前神经管缺损。这种有条件的Irf6等位基因的产生允许对颅面发育的新见解和对Irf6的产后作用的新探索。
