Aryal Neeraj K, Wasylishen Amanda R, Pant Vinod, Riley-Croce Maurisa, Lozano Guillermina
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Genes and Development Program, The University of Texas MD Anderson Cancer Center, UT Health Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
Oncotarget. 2017 Oct 26;8(61):103996-104006. doi: 10.18632/oncotarget.22087. eCollection 2017 Nov 28.
Increased levels of inhibitors of the p53 tumor suppressor such as Mdm2 and Mdm4 drive tumor development and thus serve as targets for therapeutic intervention. Recently, digestive organ expansion factor (Diexf) has been identified as a novel inhibitor of p53 in zebrafish. Here, we address the potential role of Diexf as a regulator of the p53 pathway in mammals by generating knockout mice. We demonstrate that, similar to and , homozygous deletion of is embryonic lethal. However, unlike in and mice, loss of p53 does not rescue this phenotype. Moreover, heterozygous animals are not sensitive to sub-lethal ionizing radiation. Thus, we conclude that is an essential developmental gene in the mouse, but is not a significant regulator of the p53 pathway during development or in response to ionizing radiation.
诸如Mdm2和Mdm4等p53肿瘤抑制因子水平的升高会驱动肿瘤发展,因此可作为治疗干预的靶点。最近,消化器官扩张因子(Diexf)已被鉴定为斑马鱼中一种新型的p53抑制剂。在此,我们通过构建基因敲除小鼠来研究Diexf作为哺乳动物p53通路调节因子的潜在作用。我们证明,与[此处原文可能缺失相关基因名称]和[此处原文可能缺失相关基因名称]类似,Diexf的纯合缺失是胚胎致死性的。然而,与[此处原文可能缺失相关基因名称]和[此处原文可能缺失相关基因名称]小鼠不同,p53的缺失并不能挽救这种表型。此外,Diexf杂合动物对亚致死剂量的电离辐射不敏感。因此,我们得出结论,Diexf是小鼠中的一个必需发育基因,但在发育过程中或对电离辐射的反应中不是p53通路的重要调节因子。