The GMPPA Knockout Raji Polyclonal Cells are a CRISPR/Cas9-mediated gene disruption model in the human Burkitt lymphoma-derived Raji B lymphocyte line. This product comprises a polyclonal population of edited cells carrying loss-of-function mutations in GMPPA, the gene encoding GDP-mannose pyrophosphorylase A. By disrupting GMPPA, researchers can examine the consequences of impaired GDP-mannose biosynthesis on glycoconjugate assembly and B-cell function.
Raji is an Epstein-Barr virus (EBV)-positive B lymphocyte cell line widely employed to study antibody production, antigen presentation, and adaptive immune signaling. Derived from a Burkitt lymphoma, Raji cells express characteristic surface receptors and are susceptible to apoptosis modulation, making them a robust platform for investigating glycosylation-dependent B-cell biology and lymphomagenesis.
GMPPA functions as the catalytic subunit of a heteromeric complex with GMPPB, catalyzing the conversion of mannose-1-phosphate and GTP into GDP-mannose, the activated mannose donor for glycosylation. GMPPA expression is regulated by the SP1 transcription factor and is responsive to cellular energy status and mannose availability. GDP-mannose serves as a substrate for mannosyltransferases including ALG1 in the dolichol pathway, POMT1 for O-mannosylation, and GPI mannosyltransferases for GPI anchor biosynthesis. Disruption of GMPPA depletes GDP-mannose pools, thereby impairing N-glycan precursor assembly, O-mannosyl glycoprotein modification, and GPI anchor synthesis.
In Raji B cells, glycosylation is critical for proper folding, trafficking, and function of surface receptors such as the B-cell receptor (BCR). GMPPA knockout likely compromises N-glycan, O-mannosyl, and GPI-anchored protein modifications, potentially altering BCR signaling, antibody secretion, and immune recognition. This model enables elucidation of mannose metabolism??s role in B-cell malignancies, immune responses, and glycosylation-dependent survival mechanisms.
This knockout product is applicable to studies of GMPPA-associated congenital disorders of glycosylation (GMPPA-CDG), Burkitt lymphoma glycosylation dependencies, and drug target exploration. Representative assays include western blotting and RT-qPCR for GMPPA disruption confirmation, lectin blotting and mass spectrometry-based glycomics for global glycan changes, flow cytometry for surface glycan profiling, phospho-flow analysis of BCR signaling, apoptosis assays, and metabolic labeling with mannose analogues. For further technical information, please contact Ascent Research.
