The ABCC3 Knockout Jurkat Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Jurkat T lymphocyte line, designed to disrupt the ABCC3 gene. This loss-of-function model enables rigorous investigation of ABCC3-dependent transport mechanisms without relying on single-cell clonal isolation, thus capturing population-level heterogeneity. ABCC3 (ATP-binding cassette subfamily C member 3), also known as MRP3, encodes an organic anion transporter implicated in multidrug resistance and bile acid homeostasis. The polyclonal format ensures representation of diverse editing outcomes, offering a robust tool for pooled functional studies.
Jurkat cells are an immortalized human T lymphocyte line derived from a patient with T cell acute lymphoblastic leukemia (T-ALL), widely used to model T cell signaling, leukemia biology, and immune cell pharmacology. These suspension cells grow rapidly and are amenable to high-throughput drug screening and genetic manipulation. Their leukemic origin makes them particularly relevant for studying overexpression or knockout of transporters involved in chemoresistance. The Jurkat background constitutively activates key signaling cascades such as PI3K/AKT and MAPK pathways, which intersect with ABCC3 regulatory networks. Consequently, this knockout model provides a defined genetic context to dissect transporter function in a leukemic T cell environment.
ABCC3 is an ATP-binding cassette transporter that effluxes organic anions, bile acids, and xenobiotic conjugates. Its expression is regulated by nuclear receptors PXR (NR1I2), CAR (NR1I3), and FXR (NR1H4), and by the oxidative stress sensor NRF2 (NFE2L2). PI3K/AKT and MAPK signaling converge on these transcriptional regulators. Downstream, ABCC3 exports glucuronide conjugates and chemotherapeutic agents, thereby reducing intracellular drug accumulation. The transporter interacts with NHERF1 (SLC9A3R1) for membrane localization. Knockout ablates this efflux, causing substrate accumulation.
In Jurkat cells, ABCC3 knockout eliminates a key drug export pathway, sensitizing these leukemia-derived cells to MRP3 substrates. This isogenic system dissects ABCC3’s contribution to multidrug resistance in T-ALL, separate from other ABC transporters. The polyclonal population mimics tumor heterogeneity, enabling study of resistance mechanisms influenced by variable ABCC3 expression. The model also permits investigation of NRF2-driven oxidative stress responses in T cell detoxification.
Applications include drug sensitization screens comparing knockout and wild-type cells to identify MRP3-substrate anticancer agents. Flow cytometry quantifies intracellular accumulation of fluorescent substrates. Co-immunoprecipitation and immunofluorescence explore ABCC3?CNHERF1 interactions. RNA-seq and Western blotting assess compensatory changes in transporter expression. Pharmacological assays with PXR or FXR ligands probe transcriptional regulation in the absence of ABCC3. For further details, contact Ascent Research.
