CBR1 Knockout HEK293T Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from HEK293T cells. The CBR1 gene is disrupted via CRISPR/Cas9-mediated gene editing, yielding a heterogeneous pool of knockout alleles. This polyclonal format avoids clonal selection artifacts and facilitates consistent functional assessments. The model supports investigation of carbonyl reductase 1-dependent processes in drug metabolism and redox regulation.
HEK293T cells, derived from human embryonic kidney, are an epithelial line that stably expresses SV40 large T antigen, facilitating high-level expression from SV40 origin-containing plasmids. Their rapid proliferation, ease of transfection, and well-characterized molecular landscape make them a versatile host for gene knockout studies and pharmacological screening.
CBR1 encodes an NADPH-dependent oxidoreductase that reduces carbonyl groups on endogenous and xenobiotic substrates, including quinones, prostaglandin E2, and anthracyclines such as doxorubicin. Transcription is regulated by NRF2, HIF-1??, AhR, and CAR. CBR1 acts upstream of effectors like 4-hydroxynonenal and prostaglandin E2, interacting with NADPH and aldo-keto reductases. It functions within the PTGS2/CBR1/15-hydroxyprostaglandin dehydrogenase axis, influencing detoxification of reactive aldehydes and prostaglandin inactivation. Consequently, CBR1 knockout may enhance oxidative stress sensitivity and disrupt prostaglandin catabolism.
In HEK293T cells, CBR1 disruption permits dissection of carbonyl reductase contributions to metabolism and stress responses. Loss of function sensitizes cells to carbonyl-containing xenobiotics and anthracyclines, while perturbing prostaglandin signaling. This system provides insights into drug resistance mechanisms and the interplay between redox balance and inflammation, leveraging HEK293T suitability for high-throughput chemical biology approaches.
Key applications include drug metabolism and cytotoxicity profiling, oxidative stress analysis, and prostaglandin pathway investigation. Representative assays encompass menadione reduction kinetics, RT-qPCR and Western blotting for target validation, immunofluorescence, MTT/XTT viability tests, LC-MS metabolite monitoring, and ROS detection. Toxicology screening programs benefit from this model to assess carbonyl compound toxicity. For further information, please contact Ascent Research.
