ETHE1 Knockout Raji Polyclonal Cells are a polyclonal cell population generated by CRISPR/Cas9-mediated disruption of the ETHE1 gene in the Raji B lymphocyte cell line. This knockout model serves as a loss-of-function system for investigating ETHE1??s role in mitochondrial sulfide oxidation and sulfur metabolism. The polyclonal format maintains genetic heterogeneity, making it well-suited for bulk assays in disease-relevant studies.
The Raji cell line, originating from a Burkitt lymphoma patient, is an EBV-positive, suspension-growing human B lymphocyte model. Raji cells retain antibody production capabilities and adaptive immune features, with high proliferative and metabolic activity that sensitizes them to mitochondrial dysfunction. This background provides a physiologically relevant system for analyzing the impact of ETHE1 deficiency in a lymphoid context.
ETHE1 encodes a mitochondrial matrix persulfide dioxygenase that catalyzes the oxidation of persulfide to sulfite, a critical step in the hydrogen sulfide (H?S) detoxification pathway. Operating within the mitochondrial matrix, ETHE1 functions downstream of sulfide:quinone oxidoreductase (SQR) and cooperates with thiosulfate sulfurtransferase (TST) to convert toxic sulfide. The enzyme is transcriptionally regulated by NRF2 and HIF1A, and its reaction products sulfite and thiosulfate directly influence cytochrome c oxidase activity and overall mitochondrial respiration. Loss of ETHE1 disrupts sulfide homeostasis, leading to accumulation of H?S, ethylmalonic aciduria, and severe mitochondrial respiratory chain inhibition, hallmarks of ethylmalonic encephalopathy.
In Raji B cells, ETHE1 knockout faithfully models mitochondrial sulfur metabolism defects. The resulting sulfide toxicity elevates reactive oxygen species levels and triggers apoptosis, while impairing cellular energetics due to reduced cytochrome c oxidase function. Given the high metabolic demands of B cells for antibody synthesis and proliferation, this model offers unique insights into the mitochondrial-immune axis and the consequences of toxin accumulation on adaptive immunity.
Key research applications include disease modeling for ethylmalonic encephalopathy and Leigh syndrome, mechanistic studies of sulfide-induced mitochondrial damage, and drug screening to identify sulfide detoxification enhancers. Compatible assays include Western blotting to confirm ETHE1 protein loss, LC-MS quantification of sulfide metabolites, Seahorse respirometry for mitochondrial function, ROS detection, and apoptosis assays. These polyclonal knockout cells provide a reproducible and accessible platform for academic and pharmaceutical research. For further technical details or custom orders, please contact Ascent Research.
