The GSTM2 Knockout HEK293T Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HEK293T human embryonic kidney cell line. Targeted disruption of GSTM2 ablates glutathione S-transferase mu 2 activity, creating a versatile loss-of-function model for investigating detoxification pathways and oxidative stress signaling.
HEK293T cells are an adenovirus 5-transformed HEK293 derivative expressing SV40 large T antigen, enabling episomal plasmid replication and high-level transient expression. Their epithelial morphology and renal origin make them a physiologically relevant model for toxicology and kidney biology. Widely used for viral production and genetic engineering, HEK293T cells provide a robust platform for knockout studies, with high transfection efficiency facilitating downstream complementation and reporter assays.
GSTM2 catalyzes glutathione (GSH) conjugation to electrophilic xenobiotics and endogenous metabolites, neutralizing their reactivity and promoting excretion. Expression is induced by NRF2 and AhR in response to oxidative stress and electrophilic compounds. The enzyme directly reduces ROS and electrophilic intermediates, protecting cells from oxidative damage. Additionally, GSTM2 binds ASK1 and JNK1, inhibiting MAPK cascade activation and downstream NF-??B signaling, thereby modulating apoptosis and inflammation. The glutathione pathway includes glutamate-cysteine ligase for GSH synthesis and glutathione reductase for maintaining reduced GSH pools.
In HEK293T cells, GSTM2 knockout sensitizes to electrophilic and oxidative stresses, highlighting its role in chemoresistance. This model is valuable for assessing drug sensitivity, particularly to alkylating and platinum agents, and for studying NRF2-mediated stress adaptation. The epithelial background supports investigation of renal detoxification and environmental electrophile toxicity. Complementation with GSTM2 variants enables structure-function analyses, and the knockout facilitates synthetic lethality screens in glutathione-depleted conditions.
Applications include drug metabolism studies, oxidative stress assays, and cancer drug resistance research. Key techniques involve Western blotting and RT-qPCR for knockout confirmation, glutathione S-transferase activity assays, ROS flow cytometry, and drug sensitivity testing under oxidative challenge. The cells enable high-throughput screening of electrophilic compounds and LC-MS-based metabolite profiling. NRF2 reporter assays can probe upstream regulatory pathways. For technical inquiries, please contact Ascent Research.
