The GRHPR Knockout Jurkat Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population targeting the GRHPR gene in Homo sapiens Jurkat T lymphocytes. This knockout model enables loss-of-function studies of glyoxylate reductase/hydroxypyruvate reductase in a leukemia-derived cell background. The polyclonal nature reflects diverse editing events, suitable for population-level analyses.
Jurkat cells are an acute T cell leukemia-derived line widely used to study T cell receptor signaling, apoptosis, and cancer biology. These suspension-adapted cells offer a well-characterized system for genetic manipulation, providing a relevant context for exploring gene function in T lymphocyte physiology and malignant transformation.
GRHPR encodes glyoxylate reductase/hydroxypyruvate reductase, catalyzing the NADPH-dependent reduction of glyoxylate to glycolate and hydroxypyruvate to D-glycerate. This enzyme is central to glyoxylate detoxification and intersects with serine/glycine metabolism. Its activity is regulated by PPAR?? signaling and substrate availability, primarily glyoxylate and hydroxypyruvate. Within the metabolic network, GRHPR functions downstream of glycolate oxidase (GO) and alanine-glyoxylate aminotransferase (AGT). The cofactor NADPH is indispensable for its reductase activity, and substrate-dependent interactions govern kinetics. Knockout of GRHPR eliminates glyoxylate reductase activity, disrupting glyoxylate detoxification and leading to decreased production of glycolate and D-glycerate, while oxalate accumulation may increase, phenocopying the metabolic disturbance of primary hyperoxaluria type 2.
In the Jurkat T lymphocyte model, GRHPR knockout enables the study of oxalate-induced metabolic stress within an immune cell context, revealing potential linkages between glyoxylate metabolism and T cell function. This model facilitates investigation of how GRHPR deficiency affects T cell proliferation, activation, and survival, as well as redox balance and metabolic reprogramming in leukemic cells. The polyclonal population captures the genetic heterogeneity observed in tumors, allowing robust analysis of population-level metabolic responses to glyoxylate pathway disruption.
Researchers can employ this model for studying primary hyperoxaluria type 2, screening compounds that modulate glyoxylate metabolism, and assessing oxalate toxicity in T cells. Validation methods include Western blotting and RT-qPCR for GRHPR expression, glyoxylate reductase activity assays, intracellular oxalate measurement, and cell viability tests under glyoxylate stress. Metabolomics can reveal broader pathway alterations. For inquiries, contact Ascent Research.
