The DKKL1 knockout HAP1 polyclonal cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the gene encoding Dickkopf-related protein 1 (DKKL1) has been disrupted. Supplied as a mixed population of HAP1 cells harboring heterogeneous loss-of-function mutations at the DKKL1 locus, this product avoids the bottleneck effects associated with single-cell cloning while providing a representative knockout model suitable for pooled experimental approaches.
The parental HAP1 cell line is a human near-haploid fibroblast-like line derived from the KBM-7 CML line, which carries the Philadelphia chromosome and expresses BCR-ABL1. HAP1 cells grow as an adherent monolayer and retain a near-haploid karyotype, except for disomy of chromosome 8. This unique genetic background was originally established for haploid genetic screens and has become a widely adopted platform for CRISPR-based functional genomics, enabling efficient genome editing and direct genotype-phenotype correlation in a cancer-relevant context.
DKKL1 encodes a secreted glycoprotein of the Dickkopf-related family, structurally related to canonical Wnt modulators but with distinct biochemical properties. The protein is proposed to interact with LRP6 and Frizzled co-receptors, modulating ??-catenin stability and Wnt/??-catenin transcriptional outputs. DKKL1 also engages PI3K/AKT signaling, promoting AKT phosphorylation and upregulation of Cyclin D1 (CCND1), MMP9, and the EMT regulator Snail. Upstream regulatory inputs include the transcription factor SOX2 and the Wnt ligand Wnt3a, positioning DKKL1 at a convergence point for developmental and oncogenic pathways.
In the context of the HAP1 near-haploid model, disruption of DKKL1 offers a powerful system to dissect its contributions to Wnt and PI3K/AKT pathway activity, simplifying interpretation of loss-of-function phenotypes without confounding effects from a second allele. Although HAP1 cells are leukemia-derived, the pleiotropic roles of DKKL1 in proliferation, migration, and spermatogenesis make this knockout population broadly relevant for studying mechanisms operative in Wnt-driven solid tumors such as lung and colorectal cancers. The absence of a wild-type DKKL1 allele in the polyclonal pool permits robust assessment of pathway perturbations in response to upstream stimuli or pharmacological inhibitors.
This DKKL1 knockout HAP1 polyclonal cell population is suitable for wide-ranging research applications, including high-throughput genetic screens to identify Wnt signaling modulators. Typical assays include phospho-AKT Western blotting, scratch wound migration assays, MTT proliferation assays, and RT-qPCR for CCND1 and MMP9. The population is also compatible with TOP/FOP Flash reporter assays to measure Wnt/??-catenin transcriptional activity. These approaches facilitate dissection of DKKL1-dependent signaling networks and support identification of therapeutic targets in Wnt-related cancers. For further information, please contact Ascent Research.
