The DOCK4 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from HAP1 cells, offering a loss-of-function model for the DOCK4 gene. This product provides a heterogeneous pool of cells with targeted disruption of DOCK4, enabling functional studies without wild-type protein expression. The knockout is achieved through CRISPR/Cas9-mediated gene disruption, and the polyclonal format allows for immediate use in diverse assays, including biochemical and cell-based analyses.
HAP1 is a near-haploid human cell line originating from the KBM-7 chronic myeloid leukemia line. Its haploid karyotype simplifies gene editing, as mutation of a single allele yields a complete knockout. HAP1 cells are widely utilized in functional genomics and knockout screening due to their genetic tractability and stable growth. They retain key signaling pathways governing cell adhesion, migration, and cytoskeletal regulation, making them a suitable host for studying DOCK4 function in a disease-relevant background.
DOCK4 functions as a guanine nucleotide exchange factor for Rap1, activating it by promoting GTP binding. It forms complexes with ELMO1 and ELMO2 and is regulated by upstream signals from TGF-??, Wnt ligands, and SRC family kinases. Activated Rap1 reinforces cell-cell adhesion by stabilizing E-cadherin and ??-catenin at junctions, while also modulating actin dynamics via Rac1 and Cdc42. DOCK4 loss disrupts these interactions, weakening adhesion and promoting epithelial-mesenchymal transition. Thus, DOCK4 acts as a tumor suppressor and a key regulator of cellular architecture.
In the HAP1 background, DOCK4 disruption provides a clean genetic model for dissecting its signaling roles. The haploid nature ensures complete loss of function, eliminating wild-type confounding. This system is ideal for probing DOCK4??s tumor suppressor activities and its integration of TGF-?? and Wnt signals to control adhesion and migration. The knockout cells enable mechanistic studies relevant to cancer metastasis and neurodevelopmental conditions, leveraging HAP1??s well-characterized signaling landscape.
Research applications include investigating DOCK4??s role in cancer (colorectal, lung, breast), autism spectrum disorder, and neurodevelopment. Typical assays comprise western blotting, cell adhesion and Transwell migration assays, immunofluorescence for junctional markers (E-cadherin, ??-catenin), Rap1 activity pull-downs, and RNA-seq. The model supports screening of Rap1 pathway modulators and functional studies of adhesion dynamics. For further information, contact Ascent Research.
