Livestock Biotechnology, School of Life Science, Technische Universität München, Germany.
Biochem Biophys Res Commun. 2021 May 14;553:25-29. doi: 10.1016/j.bbrc.2021.03.068. Epub 2021 Mar 18.
The current COVID-19 pandemic is caused by infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A sex-bias has been observed, with increased susceptibility and mortality in male compared to female patients. The gene for the SARS-CoV-2 receptor ACE2 is located on the X chromosome. We previously generated TP53 mutant pigs that exhibit a sex-specific patho-phenotype due to altered regulation of numerous X chromosome genes. In this study, we explored the effect of p53 deficiency on ACE2 expression in pigs. First, we identified the p53 binding site in the ACE2 promoter and could show its regulatory effect on ACE2 expression by luciferase assay in porcine primary kidney fibroblast cells. Later, quantitative PCR and western blot showed tissue- and gender-specific expression changes of ACE2 and its truncated isoform in p53-deficient pigs. We believe these findings will broaden the knowledge on ACE2 regulation and COVID-19 susceptibility.
当前的 COVID-19 大流行是由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）感染引起的。已经观察到一种性别偏向，与女性患者相比，男性患者的易感性和死亡率更高。SARS-CoV-2 受体 ACE2 的基因位于 X 染色体上。我们之前生成了 TP53 突变的猪，由于许多 X 染色体基因的调控改变，这些猪表现出性别特异性的病理表型。在这项研究中，我们探讨了 p53 缺失对猪 ACE2 表达的影响。首先，我们确定了 ACE2 启动子中的 p53 结合位点，并通过猪原代肾成纤维细胞中的荧光素酶测定证实了其对 ACE2 表达的调节作用。随后，定量 PCR 和 Western blot 显示，p53 缺失的猪中 ACE2 及其截断同工型在组织和性别上均存在表达变化。我们相信这些发现将拓宽 ACE2 调控和 COVID-19 易感性的知识。
