The EIF2AK1 Knockout MES-OV Polyclonal Cells are a CRISPR/Cas9-engineered polyclonal population of human ovarian mesothelial cells with targeted disruption of EIF2AK1, encoding the heme-regulated inhibitor (HRI) kinase. This polyclonal knockout model preserves cell population heterogeneity, providing a biologically relevant system for studying loss of HRI function without clonal selection artifacts.
The MES-OV line originates from human ovarian mesothelium, a tissue that lines the peritoneal cavity and contributes to secretion, inflammation, and ovarian cancer metastasis. These cells are extensively used to model mesothelial biology and tumor?Cmesothelial interactions, making them an ideal host for investigating stress pathways relevant to peritoneal malignancies.
EIF2AK1 (HRI) is a serine/threonine kinase that phosphorylates eIF2?? under conditions of heme deficiency, oxidative stress, mitochondrial dysfunction, or heat shock. This phosphorylation attenuates global cap-dependent translation while selectively upregulating ATF4 translation, which in turn induces stress-response genes such as CHOP, GADD34, and ASNS. This integrated stress response reprogramming is critical for cellular adaptation to diverse insults. HRI activity is regulated by the chaperones HSP90 and CDC37, and by small molecules including hemin and nitric oxide. Disruption of HRI abrogates this axis, blocking ATF4-mediated adaptive gene expression and altering cellular stress resilience.
In ovarian mesothelial cells, EIF2AK1 knockout enables dissection of the ISR under physiologically relevant conditions, such as oxidative stress encountered in the peritoneal environment. The model is particularly useful for studying how mesothelial cells influence ovarian cancer cell adhesion, invasion, and metastasis, and for testing therapies that target stress pathways. Additionally, given HRI??s essential role in erythropoiesis, this line can be applied to erythroid stress research and to investigate links between systemic heme metabolism and cancer progression.
Assays compatible with this product include Western blotting for phospho-eIF2??, polysome profiling, ATF4 luciferase reporters, stress challenge protocols (e.g., arsenite, thapsigargin) followed by RT-qPCR for ATF4 targets or cell viability measurements, and flow cytometry for reactive oxygen species. The polyclonal population is amenable to drug screens and CRISPR-based complementation. For additional information, please contact Ascent Research.
