The GSKIP Knockout HAP1 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population generated from the HAP1 near-haploid human cell line, featuring targeted disruption of the GSKIP gene. This pooled knockout model offers a genetically defined loss-of-function system without clonal isolation, preserving diverse editing outcomes while establishing a consistent null background suitable for pooled functional assays and genetic screening.
HAP1 is a near-haploid human cell line derived from a chronic myeloid leukemia patient, characterized by a haploid karyotype for most chromosomes. This haploid state eliminates heterozygous complications, enabling unambiguous genotype?Cphenotype correlations and simplifying gene disruption analyses. HAP1 cells are widely adopted for functional genomics, drug target validation, and large-scale CRISPR screening due to their stable adherent growth and ease of genetic manipulation.
GSKIP (GSK3B Interacting Protein) negatively regulates GSK3B kinase activity by directly binding GSK3B and competing with AXIN1, impairing ??-catenin destruction complex assembly. This inhibition stabilizes ??-catenin (CTNNB1), promoting its nuclear accumulation and TCF/LEF-mediated transcription of Wnt target genes such as MYC and CCND1. GSKIP activity is modulated by upstream regulators including WNT ligands, insulin, and growth factors, and it influences downstream effectors like tau (MAPT) and the interacting phosphatase PP2A, situating GSKIP at a critical node in Wnt signaling, insulin signaling, and neuronal differentiation.
In the HAP1 near-haploid context, GSKIP knockout creates a clean null background for investigating constitutive GSK3B inhibition and Wnt pathway activation. The absence of a second allele ensures complete loss of protein function, facilitating dissection of GSKIP??s role in proliferation, differentiation, and drug response. This model is particularly relevant for studying cancers driven by aberrant Wnt/??-catenin signaling, as well as neurodevelopmental disorders and schizophrenia linked to GSK3B dysregulation.
Key applications include assessing ??-catenin stabilization and TCF/LEF activity via western blotting and luciferase reporter assays, probing GSK3B?CGSKIP interactions by co-immunoprecipitation, visualizing ??-catenin nuclear localization through immunofluorescence, and quantifying Wnt target gene expression by RT-qPCR. The polyclonal pool is ideal for CRISPR-based genetic screens and pooled functional genomics, enabling systematic interrogation of GSKIP-dependent processes. For further details or to initiate a quote, please reach out to Ascent Research.
