Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Immunol Cell Biol. 2017 Sep;95(8):676-683. doi: 10.1038/icb.2017.35. Epub 2017 Apr 21.
The biological role of granzyme K, a serine protease of cytotoxic T lymphocytes (CTL), is controversial. It has been reported to induce perforin-mediated cell death in vitro, but is also reported to be non-cytotoxic and to operate in inflammatory processes. To elucidate the biological role of this protease, we have deleted the granzyme K gene in mice (mutant allele: Gzmk; MGI:5636646). Gzmk mice are healthy, anatomically normal, fecund and show normal hematopoietic development. Gzmk mice readily recover from lymphocytic choriomeningitis virus and mouse pox Ectromelia virus infection. Ex vivo, virus-specific granzyme K-deficient CTL are indistinguishable from those of wild-type mice in apoptosis induction of target cells. These data suggest that granzyme K does not play an essential role in viral immunity or cytotoxicity. Our granzyme K knockout line completes the collection of mouse models for the human granzymes, and will further our understanding of their biological roles and relationships.
颗粒酶 K 是细胞毒性 T 淋巴细胞 (CTL) 中的一种丝氨酸蛋白酶，其生物学作用存在争议。有报道称它可在体外诱导穿孔素介导的细胞死亡，但也有报道称其无细胞毒性，并在炎症过程中发挥作用。为了阐明这种蛋白酶的生物学作用，我们在小鼠中敲除了颗粒酶 K 基因（突变等位基因：Gzmk；MGI:5636646）。Gzmk 小鼠健康、解剖结构正常、繁殖力正常且造血发育正常。Gzmk 小鼠在淋巴细胞性脉络丛脑膜炎病毒和小鼠痘病毒感染后能迅速恢复。在体外，病毒特异性颗粒酶 K 缺陷型 CTL 在诱导靶细胞凋亡方面与野生型小鼠无明显差异。这些数据表明，颗粒酶 K 在病毒免疫或细胞毒性中不起关键作用。我们的颗粒酶 K 敲除系完成了人类颗粒酶的小鼠模型的收集，将进一步加深我们对它们的生物学作用和相互关系的理解。
