The DVL2 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed for targeted disruption of the DVL2 gene in the HAP1 human chronic myeloid leukemia cell line. This loss-of-function model is generated using CRISPR/Cas9-mediated gene disruption, providing a heterogeneous polyclonal pool suitable for functional genomic studies without the need for monoclonal isolation. The knockout population enables robust interrogation of DVL2-dependent signaling mechanisms and is a versatile tool for Wnt pathway research and cancer biology applications.
The HAP1 host cell line is a near-haploid human chronic myeloid leukemia (CML) model derived from the KBM-7 parental line. It exhibits adherent, fibroblast-like morphology and a largely haploid karyotype, which simplifies genetic manipulation and reduces functional redundancy, making it particularly advantageous for knockout studies. This cell line is widely used as a leukemia model and its genetic tractability supports high-throughput screening and precise dissection of signaling pathways.
DVL2 (Dishevelled 2) is a central scaffold protein that transduces Wnt signals upon Frizzled receptor activation. In the canonical Wnt/??-catenin pathway, DVL2 is phosphorylated by CK1 and GSK3??, leading to inhibition of the destruction complex composed of AXIN, APC, and GSK3??, thereby allowing ??-catenin stabilization and nuclear translocation to activate TCF/LEF-dependent transcription of target genes such as MYC, CCND1, and AXIN2. In non-canonical pathways, DVL2 interacts with ROR2 and RYK to regulate planar cell polarity via VANGL and PRICKLE, and modulates cytoskeletal dynamics through RhoA and RAC1. DVL2 also forms complexes with DVL1 and DVL3, integrating upstream Wnt ligand signals (e.g., Wnt3a, Wnt5a) through Frizzled receptors and LRP5/6 co-receptors.
In the HAP1 leukemia background, DVL2 knockout provides a well-defined model to examine Wnt signaling contributions to cancer cell proliferation, migration, and survival. The near-haploid genome facilitates loss-of-function analysis with minimal off-target effects, while the CML origin allows study of Wnt pathway dysregulation in hematological malignancies. This knockout population is particularly valuable for dissecting DVL2-specific functions independently of DVL1 and DVL3, and for evaluating its roles in ??-catenin-dependent and -independent processes within a malignant context.
Research applications include Western blotting for ??-catenin stabilization and DVL2 phosphorylation, TOP/FOP Flash luciferase reporter assays for TCF/LEF activity, RT-qPCR quantification of Wnt target genes, and co-immunoprecipitation of DVL2 interaction partners. Functional studies can employ migration and invasion assays to assess non-canonical pathway outputs, while RNA sequencing enables transcriptome-wide pathway analysis. This polyclonal DVL2 knockout cell model supports target validation, drug screening, and mechanistic investigations in Wnt-driven cancers. For additional information or custom requests, please contact Ascent Research.
