The GSTZ1 Knockout Jurkat Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population of Jurkat T lymphoblastoid cells with targeted disruption of the GSTZ1 gene. This knockout abolishes maleylacetoacetate isomerase activity, creating a loss-of-function model for studying tyrosine catabolism and glutathione-dependent detoxification. The polyclonal nature provides a heterogeneous edited pool without single-cell cloning, suitable for studies where clonal uniformity is not required.
Jurkat cells are an immortalized human T lymphocyte line derived from a 14-year-old male with acute T cell leukemia. They serve as a widely used model for CD4+ T cell biology, including T cell receptor signaling, apoptosis, and immune responses. Their robust suspension growth and well-characterized pathways make them an ideal host for investigating metabolic gene functions in lymphocytes.
GSTZ1 encodes maleylacetoacetate isomerase, a critical enzyme in the tyrosine degradation pathway that catalyzes the glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate. This reaction is essential for the proper metabolism of tyrosine and phenylalanine. Additionally, GSTZ1 possesses glutathione peroxidase activity and participates in the detoxification of xenobiotics, including the drug dichloroacetate. The enzyme is transcriptionally controlled by upstream regulators Nrf2, AhR, PPAR??, and the repressor BACH1, and it functions within a pathway involving tyrosine, homogentisate, maleylacetoacetate, and fumarylacetoacetate. GSTZ1 interacts directly with glutathione, maleylacetoacetate, and succinylacetone, and forms homodimers. Its downstream products include fumarylacetoacetate, fumarate, acetoacetate, and glutathione-conjugated xenobiotics. Disruption of GSTZ1 blocks this metabolic step, causing accumulation of maleylacetoacetate and succinylacetone, and profoundly alters redox homeostasis and electrophile-detoxification capacity.
In the Jurkat T-cell context, loss of GSTZ1 creates a human-relevant model to investigate the intersections of tyrosine catabolism, glutathione metabolism, and lymphocyte function. The knockout enables researchers to dissect the Nrf2/ARE-mediated antioxidant response and AhR-driven detoxification pathways. Because Jurkat cells possess active signaling networks for apoptosis and immune activation, this model is valuable for studying how accumulation of toxic metabolites like succinylacetone affects T cell viability, redox balance, and drug sensitivity.
This polyclonal knockout cell population is suitable for a wide range of experiments, including modeling tyrosinemia type III-like metabolic disorders, mechanistic analyses of tyrosine degradation, and toxicological evaluations of dichloroacetate and other xenobiotics. Key assays include Western blotting and RT-qPCR for knockout confirmation, maleylacetoacetate isomerase activity measurements, LC-MS metabolomic profiling of tyrosine pathway intermediates, glutathione level quantification, cell viability tests under oxidative stress, drug sensitivity assays, and flow cytometric assessment of apoptosis and reactive oxygen species. The model offers a defined system for exploring GSTZ1 function in metabolism and detoxification. For further technical information, please contact Ascent Research.
