Gsdmc-flox Mouse

Gsdmc, short for gasdermin C, is a member of the gasdermin family. Pyroptosis, a form of regulated cell death, is one of its key associated functions. It can be involved in pathways such as caspase-8-mediated cleavage, which is associated with metabolite-induced pyroptosis, and may also play a role in PD-L1-mediated switching of apoptosis to pyroptosis in cancer cells. Gsdmc is thus of importance in understanding cell death mechanisms and related biological processes [1,3].

Depletion of Gsdmc in pancreatic adenocarcinoma cells inhibits their proliferation, invasion, and migration, suggesting Gsdmc may promote the growth and spread of this cancer type [2]. In colon epithelial cells, the lack of N6-adenosine methyltransferase subunit Mettl14 disrupts N6-adenomethylation on GsdmC transcripts, abolishes GsdmC expression, and leads to apoptosis of Lgr5+ stem cells, impairing colon mucosal morphogenesis [4]. Also, in cancer models, GSDMC sensitizes tumor cells to PARP inhibitor therapy, promoting tumor clearance independent of BRCA deficiency, and increasing memory CD8+ T cell population and cytotoxic CD8+ T cell infiltration [5].

In summary, Gsdmc plays essential roles in processes like cell death regulation, tumor cell behavior, and maintaining normal colonic epithelial morphogenesis. Mouse models with Gsdmc-related manipulations, such as gene knockout or conditional knockout, have provided insights into its functions in pancreatic adenocarcinoma, colonic epithelial development, and cancer response to PARP inhibitor therapy, highlighting its potential as a therapeutic target in these disease areas.