KHDRBS1 Knockout HAP1 Polyclonal Cells provide a CRISPR/Cas9-edited polyclonal knockout population targeting the KHDRBS1 gene (encoding Sam68) in the HAP1 cell background. This heterogeneous pool contains cells with targeted gene disruptions, enabling loss-of-function analysis free from clonal selection biases. It serves as a versatile model for studying KHDRBS1-dependent processes in signal transduction, splicing regulation, and haploid genetic screens.
The HAP1 cell line is a near-haploid human cell line derived from the chronic myeloid leukemia (CML) cell line KBM-7. Its stable haploid karyotype simplifies CRISPR-based gene editing by targeting a single allele, minimizing compensatory effects and facilitating clean knockout phenotypes. HAP1 cells are adherent and retain key leukemic signaling pathways, making them an ideal platform for genetic screens and functional genomics.
KHDRBS1 (Sam68) is an RNA-binding protein that couples tyrosine kinase signaling to RNA processing. It is phosphorylated by SRC-family kinases (FYN and SRC) and ERK1/2 upon growth factor stimulation, modulating its interaction with RNA and spliceosome components. This regulation alters alternative splicing of targets such as Bcl-x (controlling apoptosis), CD44, and tau, as well as translation of Cyclin D1. Through these mechanisms, KHDRBS1 links extracellular signals to cell cycle progression, apoptosis, and proliferation. Interacting partners include GRB2, PLCG1, and SH3 domain-containing proteins.
Disruption of KHDRBS1 in the HAP1 near-haploid background offers a genetically tractable model for dissecting signaling-dependent splicing and cell fate decisions. Given its CML origin, this knockout population is particularly relevant for leukemia studies, though KHDRBS1 dysregulation is also implicated in breast, glioblastoma, and prostate cancers. The polyclonal format captures a spectrum of loss-of-function effects while leveraging haploid genetics for robust phenotype comparisons against wild-type HAP1 cells.
This knockout model supports diverse applications: cancer biologists can validate Sam68 contributions to tumor cell survival; signal transduction researchers can analyze ERK/MAPK and PI3K/AKT pathways via phospho-specific western blotting; splicing studies employ RT-PCR for Bcl-x and CD44 isoforms or RNA immunoprecipitation. The haploid background enables high-throughput genetic and drug sensitivity screens. Additional readouts include flow cytometry for apoptosis markers, cell cycle analysis, and proliferation assays. Contact Ascent Research for further details.
