The ABCC1 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the HAP1 human near-haploid cell line. This product features a targeted disruption of ABCC1, which encodes the multidrug resistance protein 1 (MRP1). The polyclonal population contains diverse editing events, providing a functional loss-of-function model without clonal isolation. Supplied as a suspension culture, these cells are immediately suitable for expansion and downstream assays. This model enables investigation of ABCC1-dependent transport and its role in drug sensitivity and detoxification.
HAP1 is a human near-haploid chronic myeloid leukemia (CML) cell line derived from a 39-year-old male patient. With a near-haploid karyotype, it grows in suspension and retains myeloid progenitor features, making it a robust hematopoietic model for genetic studies. Its simplified genome reduces redundancy, aiding clear interpretation of knockout effects. HAP1 cells are well-suited for high-throughput screening and flow cytometry, and this background is particularly relevant for studying membrane transporters and drug resistance in a leukemic context.
ABCC1 (MRP1) is an ATP-dependent efflux pump that transports glutathione conjugates, xenobiotics, LTC4, and chemotherapeutic drugs, operating within glutathione conjugation and drug metabolism pathways. Its expression is regulated by NRF2, NF-??B, p53, and MYC, with signaling through PI3K/AKT and MAPK pathways in response to oxidative stress and chemotherapeutic agents. Downstream substrates include glutathione conjugates, oxidized glutathione, cAMP, cGMP, and drugs like methotrexate and vincristine. ABCC1 interacts with RLIP76, PDZK1, and the actin cytoskeleton, influencing its localization and activity.
In the HAP1 CML background, ABCC1 knockout impairs efflux of toxic compounds, increasing intracellular drug retention and sensitizing cells to chemotherapeutics. This is particularly relevant for multidrug resistance studies in hematological malignancies. The near-haploid nature ensures unambiguous knockout effects, while the polyclonal population mimics tumor heterogeneity, aiding adaptive resistance studies. Combining ABCC1 loss with the leukemic HAP1 background allows dissection of MRP1’s role in drug resistance and detoxification.
This product supports diverse applications, from mechanistic studies of multidrug resistance to high-throughput screening of transporter substrates and inhibitors. Users can validate ABCC1 disruption via Western blotting and RT-qPCR, measure transport activity by calcein-AM efflux flow cytometry, and assess drug sensitivity with MTS/MTT assays. Additionally, glutathione quantification and LTC4 transport assays provide functional readouts, while RNA-seq can identify compensatory pathways. For culture conditions, validation data, or application support, please contact Ascent Research.
