DSG4 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HAP1 near-haploid human cell line. These cells carry a targeted disruption of the DSG4 gene, resulting in loss of desmoglein 4 protein expression, providing a reliable loss-of-function model for studying desmosome-dependent cell adhesion and related signaling pathways.
HAP1 is a male, near-haploid fibroblast-like cell line originating from KBM-7 chronic myelogenous leukemia cells, widely employed as a leukemia model and a powerful genetic screening tool due to its haploid nature that simplifies gene editing and phenotypic analysis. Its robust growth and adaptability to high-throughput assays make it an ideal host for generating knockout populations for functional genomics studies.
DSG4 encodes desmoglein 4, a calcium-dependent desmosomal cadherin critical for maintaining hair shaft integrity and epidermal cohesion. It functions within desmosome complexes by interacting with plakoglobin, plakophilin, and desmoplakin, which link to cytokeratin filaments. DSG4 is transcriptionally regulated by LEF1/TCF downstream of Wnt signaling and is responsive to calcium and EGFR pathways. Knockout of DSG4 disrupts desmosome assembly, potentially promoting epithelial-to-mesenchymal transition and impairing hair follicle development, as observed in monilethrix and other hair disorders.
In the HAP1 background, DSG4 knockout provides a clean genetic system to dissect desmosomal adhesion mechanisms without interference from a diploid genome, enabling precise interrogation of cell-cell adhesion, cadherin signaling, and the roles of plakoglobin and beta-catenin in both normal keratinocyte biology and cancer cell invasion. This model is particularly valuable for investigating how desmosome loss contributes to head and neck squamous cell carcinoma and alopecia-related pathologies.
Applications include hair follicle biology, desmosome functional studies, monilethrix disease modeling, and drug screening for hair disorders. Researchers can assess DSG4 protein levels via Western blotting, examine desmosome integrity by immunofluorescence, or quantify mRNA by RT-qPCR. Functional assays such as cell adhesion, scratch wound healing, and co-immunoprecipitation with plakoglobin can elucidate protein?Cprotein interactions. Additionally, proliferation assays, RNA-seq, and drug sensitivity tests support cancer research and high-throughput phenotypic screens. For further information, please contact Ascent Research.
