The GMPR2 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphocyte line, designed for functional studies of guanosine monophosphate reductase 2 (GMPR2). This product provides a heterogeneous pool of cells with targeted disruption of the GMPR2 gene, enabling interrogation of its role in purine nucleotide metabolism and GTP-dependent signaling pathways within a lymphoblastoid context.
The parental Raji cell line is an Epstein-Barr virus (EBV)-positive B lymphocyte model originally isolated from a Burkitt lymphoma patient. Raji cells exhibit suspension growth and retain key features of B cell biology, including active B cell receptor signaling and deregulated c-Myc expression, making them a widely used system for investigating lymphomagenesis, B cell signaling cascades, and the molecular basis of EBV-driven transformation.
GMPR2 encodes a NADPH-dependent oxidoreductase that catalyzes the deamination of guanosine monophosphate (GMP) to inosine monophosphate (IMP), a critical step in purine nucleotide interconversion and the regulation of GTP/ATP homeostasis. GMPR2 operates within a network that includes inosine monophosphate dehydrogenase (IMPDH) and guanosine monophosphate synthetase (GMPS), and is transcriptionally regulated by c-Myc and E2F1. Disruption of GMPR2 expression impedes the conversion of GMP to IMP, leading to an imbalance in guanine and adenine nucleotide pools, which can in turn dysregulate GTP-dependent signaling modules and downstream nucleotide-dependent processes.
In the context of Raji B lymphocytes, GMPR2 knockout offers a valuable model to dissect how purine metabolic flux supports malignant B cell proliferation and survival. Given the reliance of Burkitt lymphoma on c-Myc-driven metabolic reprogramming, loss of GMPR2 may reveal vulnerabilities in nucleotide synthesis pathways that are co-opted during lymphomagenesis. This polyclonal knockout pool enables population-level analysis of metabolic adaptation, GTP-dependent signal transduction, and sensitivity to nucleotide synthesis inhibitors, providing insights into the interplay between oncogenic signaling and purine metabolism.
Researchers can employ these cells in a variety of assays including LC-MS-based metabolomic profiling of nucleotide pools, MTS or BrdU proliferation assays, Annexin V apoptosis detection, flow cytometric cell cycle analysis, and RNA-seq transcriptomic studies. Applications range from basic investigation of GMPR2 function in purine metabolism and GTP/ATP homeostasis to translational research on lymphoma progression and drug screening for inhibitors such as methotrexate and mycophenolic acid. The model also serves as a platform for studying the pathobiology of retinitis pigmentosa, where GMPR2 mutations are implicated. For further information and ordering, please contact Ascent Research.
