The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Department of Medical Biology, The University of Melbourne, Melbourne, VIC, 3052, Australia.
Cell Death Dis. 2023 Mar 27;14(3):214. doi: 10.1038/s41419-023-05751-x.
The cytokine TNF has essential roles in immune defence against diverse pathogens and, when its expression is deregulated, it can drive severe inflammatory disease. The control of TNF levels is therefore critical for normal functioning of the immune system and health. We have identified GPATCH2 as a putative repressor of Tnf expression acting post-transcriptionally through the TNF 3' UTR in a CRISPR screen for novel regulators of TNF. GPATCH2 is a proposed cancer-testis antigen with roles reported in proliferation in cell lines. However, its role in vivo has not been established. We have generated Gpatch2 mice on a C57BL/6 background to assess the potential of GPATCH2 as a regulator of Tnf expression. Here we provide the first insights into Gpatch2 animals and show that loss of GPATCH2 affects neither basal Tnf expression in mice, nor Tnf expression in intraperitoneal LPS and subcutaneous SMAC-mimetic injection models of inflammation. We detected GPATCH2 protein in mouse testis and at lower levels in several other tissues, however, the morphology of the testis and these other tissues appears normal in Gpatch2 animals. Gpatch2 mice are viable, appear grossly normal, and we did not detect notable aberrations in lymphoid tissues or blood cell composition. Collectively, our results suggest no discernible role of GPATCH2 in Tnf expression, and the absence of an overt phenotype in Gpatch2 mice warrants further investigation of the role of GPATCH2.
细胞因子 TNF 在针对多种病原体的免疫防御中具有重要作用，而当其表达失调时，它会导致严重的炎症性疾病。因此，TNF 水平的控制对于免疫系统和健康的正常功能至关重要。我们已经确定 GPATCH2 是一种假定的 TNF 表达抑制剂，它通过 CRISPR 筛选新型 TNF 调节因子的 TNF 3'UTR 发挥转录后作用。GPATCH2 是一种拟议的癌症睾丸抗原，其在细胞系中的增殖中具有作用。然而，其在体内的作用尚未确定。我们已经在 C57BL/6 背景下生成了 Gpatch2 小鼠，以评估 GPATCH2 作为 TNF 表达调节剂的潜力。在这里，我们首次提供了关于 Gpatch2 动物的见解，并表明 GPATCH2 缺失既不会影响小鼠基础 TNF 表达，也不会影响腹腔内 LPS 和皮下 SMAC 模拟物注射炎症模型中的 TNF 表达。我们在小鼠睾丸中检测到 GPATCH2 蛋白，在其他几种组织中检测到较低水平的蛋白，然而，Gpatch2 动物的睾丸和这些其他组织的形态似乎正常。Gpatch2 小鼠是存活的，外观正常，我们没有在淋巴组织或血细胞组成中检测到明显的异常。总之，我们的结果表明 GPATCH2 在 TNF 表达中没有明显的作用，并且 Gpatch2 小鼠中没有明显的表型缺失，这使得进一步研究 GPATCH2 的作用成为必要。
