The GPATCH2L Knockout HAP1 Polyclonal Cells product provides a heterogeneous population of HAP1 cells engineered through CRISPR/Cas9-mediated disruption of the GPATCH2L gene, generating a functional knockout model for loss-of-function studies. As a polyclonal knockout cell population, this product maintains population-level genetic diversity while abrogating GPATCH2L expression, enabling robust pooled screening applications and reducing clonal bias in functional genomics experiments.
HAP1 is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia (CML) line, characterized by a haploid karyotype that facilitates gene disruption studies because only one allele typically requires targeting. This host cell line is widely adopted for genetic screens, drug sensitivity profiling, and mechanistic investigations in a CML background, providing a simplified genomic landscape for dissecting gene function in hematological malignancy contexts.
GPATCH2L encodes a G-patch domain-containing protein implicated in pre-mRNA splicing regulation through its interaction with the DHX15 RNA helicase. The protein functions within the spliceosome, forming complexes with splicing factors such as SNRNP200 and associating with core components PRPF8 and SF3B1. GPATCH2L is thought to modulate the splicing of pre-mRNAs encoding cell cycle regulators, thereby influencing gene expression programs. While its upstream regulation remains poorly characterized, MYC may regulate GPATCH2L expression in leukemia cells. The mechanistic framework places GPATCH2L downstream of transcriptional cues and upstream of mature mRNA production, with DHX15 helicase activity representing a key functional partnership.
In the HAP1 CML background, disruption of GPATCH2L perturbs spliceosome dynamics, leading to altered splicing patterns that can impact leukemia cell proliferation and viability. This model system is therefore particularly relevant for studying splicing regulation in hematological malignancies, allowing researchers to interrogate how loss of a splicing cofactor influences oncogenic gene expression programs and to identify vulnerabilities associated with splicing factor dependencies in CML.
Typical research applications include functional genomics screens to identify splicing-related dependencies, mechanistic studies of pre-mRNA processing, and phenotypic assays assessing cell proliferation and drug sensitivity??particularly imatinib sensitivity in a CML context. The knockout cells can be used in synthetic lethality screens, RNA-seq for global splicing analysis, RT-qPCR for splicing target validation, co-immunoprecipitation to confirm DHX15 interaction, and Western blotting for knockout verification. This polyclonal knockout population thus serves as a versatile tool for investigating GPATCH2L biology and splicing regulation in cancer. For further information, please contact Ascent Research.
