The DSP Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout population of HAP1 cells, offering a powerful loss-of-function model to interrogate desmoplakin biology. This product provides a heterogeneous pool of edited cells in which the DSP gene has been disrupted, enabling robust functional studies without the limitations of clonal selection. The polyclonal format ensures a diverse genetic background that mimics the complexity of in vivo cell populations, making it suitable for a broad array of biomedical research applications.
The host HAP1 cell line is a near-haploid derivative of the KBM-7 chronic myeloid leukemia (CML) cell line, representing a well-established model of CML blast crisis. Its haploid karyotype simplifies CRISPR/Cas9 editing and facilitates unambiguous genotype-phenotype correlations, rendering it an ideal chassis for generating knockout cell products. HAP1 cells retain many features of hematopoietic progenitors and are amenable to high-throughput screening and functional assays.
The DSP gene encodes desmoplakin, an essential cytolinker that anchors intermediate filaments to the desmosomal plaque, thereby maintaining tissue integrity. Desmoplakin interacts with desmosomal cadherins (desmoglein and desmocollin) and armadillo proteins (plakoglobin and plakophilin), and binds directly to keratin intermediate filaments, desmin, and vimentin. Its expression is transcriptionally regulated by TP63 and is activated by Wnt/??-catenin signaling. Downstream, desmoplakin modulates ??-catenin transcriptional activity, linking cell adhesion to signal transduction. DSP knockout disrupts desmosome assembly, impairs cell?Ccell adhesion, and uncouples cytoskeletal anchorage, contributing to arrhythmogenic right ventricular cardiomyopathy, Carvajal syndrome, and skin fragility disorders.
In the HAP1 context, DSP knockout provides a unique platform to dissect desmosome biology and Wnt pathway crosstalk in a CML blast crisis model. Although HAP1 cells are not of cardiac or epidermal origin, they express key desmosomal components and support the study of core adhesive functions and signaling mechanisms. This model is particularly valuable for investigating how desmoplakin loss alters cell migration, proliferation, and response to therapeutic agents in a leukemia-relevant background.
Researchers can leverage this product for diverse applications, including disease modeling of arrhythmogenic right ventricular cardiomyopathy and Carvajal syndrome, drug screening targeting cell adhesion pathways, and mechanistic studies of Wnt/??-catenin regulation. Routine validation can be performed via western blotting for DSP, immunofluorescence to assess desmosome integrity, cell adhesion assays, wound healing migration, and transcriptomic profiling using RNA-seq and RT-qPCR. For additional information or custom requirements, please contact Ascent Research.
