The GPM6B Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal HAP1 cell population with disruption of the GPM6B gene. This loss-of-function model comprises a heterogeneous mix of knockout alleles, enabling robust functional studies of GPM6B without requiring clonal isolation.
The HAP1 host line is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia (CML) line. These male, Philadelphia chromosome-positive cells express the BCR-ABL oncogene and grow in suspension. With only one copy of most chromosomes, HAP1 offers a simplified genomic background ideal for knockout studies, genetic screens, and cancer signaling research.
GPM6B is a neuronal membrane glycoprotein that promotes neurite outgrowth and filopodia formation by orchestrating actin cytoskeleton dynamics. It functions downstream of neurotrophin signaling: BDNF and NGF activate TrkB receptors, triggering Ras/MAPK cascades that converge on GPM6B. Additionally, retinoic acid and neuronal transcription factors SOX2 and NEUROD1 transcriptionally regulate GPM6B expression. Activated GPM6B signals through the Rho GTPases Rac1 and Cdc42, leading to actin polymerization, filopodia extension, and neurite branching. GPM6B also interacts with lipid raft proteins, flotillin, and GPM6A, and mediates homophilic adhesion, linking extracellular cues to cytoskeletal remodeling and cell adhesion.
In the HAP1 leukemia background, GPM6B knockout provides a unique tool for dissecting its roles in cell adhesion, migration, and cytoskeletal organization. While GPM6B is classically studied in neuronal development, it also contributes to glial cell biology and cancer, including glioma invasion and metastasis. The near-haploid nature of HAP1 eliminates gene-dosage effects, enabling clear attribution of phenotypes to GPM6B loss. This polyclonal model is particularly valuable for investigating how GPM6B influences BCR-ABL-driven signaling and motility in hematopoietic cells, and for identifying synthetic lethal partners in cancer.
This polyclonal knockout population supports a broad array of experimental approaches. Neurite outgrowth, cell migration, and adhesion assays directly measure GPM6B-dependent cytoskeletal changes. Protein and transcript analyses via western blotting, immunofluorescence, RNA-seq, and flow cytometry can profile altered pathways. The cells are compatible with high-throughput genetic screens and drug target validation in neurodevelopmental disorders and metastatic cancer. Genetic rescue experiments using wild-type GPM6B confirm specificity. For further information, contact Ascent Research.
