The DLGAP1 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited population of HAP1 cells carrying heterogeneous disruptions in the DLGAP1 gene, generating a polyclonal loss-of-function model. By avoiding single-cell cloning, this format preserves population diversity and minimizes clonal artifact while achieving effective target gene ablation suitable for comparative studies against wild-type counterparts. Researchers can utilize this polyclonal pool to investigate DLGAP1-dependent cellular phenotypes with enhanced statistical robustness.
HAP1 is a near-haploid cell line derived from a male chronic myeloid leukemia patient, harboring the BCR-ABL fusion. Its haploidy facilitates straightforward knockout generation and reduces genetic redundancy, making it ideal for functional genomics and signaling studies. Despite its leukemic origin, key biochemical pathways are intact, allowing investigation of non-myeloid genes through exogenous expression.
DLGAP1 (SAPAP1/GKAP) is a core postsynaptic scaffold that physically links DLG4/PSD-95 to SHANK family proteins (SHANK1-3), organizing a supramolecular complex that clusters AMPA (GRIA1-4) and NMDA (GRIN1, GRIN2A/B) receptors. Upstream signals include neuronal activity, calcium influx via NMDARs, and CAMKII-mediated phosphorylation. Downstream, DLGAP1 recruits cortactin and Homer to stabilize the actin cytoskeleton, facilitating synaptic strengthening. Disruption of DLGAP1 uncouples PSD-95 from SHANKs, leading to impaired receptor clustering and synaptic plasticity defects.
Although HAP1 cells are not of neuronal origin, they provide a valuable reductionist platform for probing the DLGAP1-PSD-95-SHANK interaction hub. The near-haploid genome simplifies knockout and enhances the reliability of comparative analyses. Researchers can study the stoichiometry, post-translational modifications, and subcellular targeting of scaffold components, as well as test the functional consequences of rare variants linked to neuropsychiatric disorders. This model also facilitates high-throughput screens to identify small molecules that disrupt or stabilize the complex.
Applications include co-immunoprecipitation for interactome mapping, immunofluorescence for spatial analysis, western blotting for expression validation, and RT-qPCR for transcript confirmation. Rescue experiments with wild-type or mutant DLGAP1 enable structure-function studies. The product supports research in synaptic biology, disease modeling for schizophrenia, autism spectrum disorder, and intellectual disability, and drug target validation. For further information, contact Ascent Research.
