The DTNBP1 Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the DTNBP1 gene has been disrupted. This polyclonal pool, generated by CRISPR/Cas9-mediated gene targeting in the K-562 leukemia cell line, provides a heterogeneous loss-of-function model for studying dysbindin-1 biology without the requirement of clonal isolation. The polyclonal format preserves population-level genetic diversity, enabling robust functional assays and minimizing clonal artifacts.
The parental K-562 cell line is a human chronic myelogenous leukemia (CML) line derived from the pleural effusion of a 53-year-old female in blast crisis. It harbors the Philadelphia chromosome and expresses the BCR-ABL1 fusion oncogene. K-562 cells are hematopoietic progenitors that spontaneously differentiate along erythroid, granulocytic, and megakaryocytic lineages, making them a versatile model for hematological differentiation, leukemia biology, and organelle biogenesis studies.
DTNBP1 encodes dysbindin-1, a core component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Dysbindin-1 interacts with other BLOC-1 subunits such as BLOC1S1, BLOC1S2, SNAPIN, PLDN, MUTED, and CNO, and with dystrobrevin (DTNA/DTNB) to regulate vesicle trafficking and lysosome-related organelle biogenesis. It functions downstream of DISC1 and AKT-mediated BDNF signaling and modulates synaptic plasticity through downstream effectors including SNAP-25, synapsin I, and NMDA receptor subunits GRIN1 and GRIN2A, and also influences dopamine D2 receptor (DRD2) trafficking and actin cytoskeleton dynamics.
In K-562 cells, which possess megakaryocytic differentiation potential, DTNBP1 knockout disrupts BLOC-1 complex function, impairing lysosome-related organelle biogenesis and vesicle trafficking. Given the role of BLOC-1 in platelet dense granule formation, this knockout model is particularly valuable for investigating the hematologic manifestations of Hermansky-Pudlak syndrome type 7 (HPS-7), which is caused by DTNBP1 mutations. The K-562 background allows direct study of dysbindin-dependent pathways in a hematopoietic context, facilitating research into the molecular mechanisms underlying dense granule deficiency and related platelet storage pool defects.
This polyclonal DTNBP1 knockout model is suited for a range of functional studies. Researchers can employ Western blotting and RT-qPCR to confirm target disruption, immunofluorescence to monitor BLOC-1 protein localization, and flow cytometry to assess hematopoietic differentiation markers. Functional assays such as ATP/ADP release tests can evaluate dense granule secretion, while migration assays probe dysbindin’s role in cell motility. The cells also support drug screening for schizophrenia-associated pathways and modeling HPS-7 pathophysiology. For additional technical specifications or ordering details, please contact Ascent Research.
