The ORMDL1 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population, derived from the human Raji B lymphocyte line, featuring targeted disruption of the ORMDL1 gene. This loss-of-function model enables investigation of ORMDL1??s role in sphingolipid metabolism, endoplasmic reticulum (ER) stress, and immune regulation without the constraints of clonal selection. The polyclonal format preserves population-level heterogeneity, offering a robust tool for functional genomic studies in a physiologically relevant B-cell context.
The Raji host cell line is an Epstein-Barr virus (EBV)-positive Burkitt??s lymphoma B lymphocyte line widely employed as a model for B cell receptor (BCR) signaling, antigen presentation, and lymphoma biology. Raji cells express functional surface immunoglobulins and are permissive for studying downstream signaling cascades that regulate proliferation, survival, and apoptosis, making them an ideal platform for dissecting gene functions in B-cell malignancies and immune responses.
ORMDL1 encodes a negative regulator of serine palmitoyltransferase (SPT), the rate-limiting enzyme in de novo sphingolipid biosynthesis. ORMDL1 physically interacts with the SPT complex (SPTLC1/2/3 and small subunits ssSPTa/b) to restrain ceramide synthesis. Under basal conditions, ORMDL1 maintains sphingolipid homeostasis; upon ER stress, sensors such as IRE1, PERK, and ATF6 alleviate ORMDL1-mediated inhibition, leading to SPT activation and elevated ceramide production. This cascade modulates downstream effectors including CHOP and BiP, linking sphingolipid flux to the unfolded protein response (UPR). Inflammatory cytokines like TNF-alpha and IL-1beta further influence ORMDL1 activity, integrating immune signals with metabolic control.
In the Raji B-cell milieu, disruption of ORMDL1 perturbs sphingolipid rheostasis, potentially altering BCR signaling thresholds, ER stress resilience, and apoptotic sensitivity. Given the lymphomagenic origin of Raji cells, this knockout model provides a unique window into how dysregulated ceramide metabolism contributes to B-cell malignancies and inflammatory disorders such as asthma and inflammatory bowel disease. The interplay between ORMDL1 and UPR pathways also implicates this model in studies of ER stress-related pathologies and metabolic regulation in lymphocytes.
Researchers can utilize these polyclonal knockout cells for quantitative sphingolipid profiling, co-immunoprecipitation of ORMDL1-SPT complexes, and western blot analysis of UPR markers like CHOP and BiP. Additional applications include flow cytometry-based assessment of apoptosis and B-cell activation, phospho-protein assays for BCR signaling, and RT-qPCR quantification of ER stress genes such as ATF4 and XBP1. This model also supports drug screening efforts aimed at modulating sphingolipid biosynthesis. For additional information or to inquire about custom cell models, please contact Ascent Research.
