The FGFR4 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited human B lymphocyte population derived from the Raji cell line, engineered to disrupt the FGFR4 gene. This polyclonal knockout model provides a heterogeneous pool of loss-of-function alleles, enabling the study of fibroblast growth factor receptor 4 signaling without the bias of single-cell cloning. The product offers a versatile tool for investigating receptor tyrosine kinase function in a lymphoblastoid background amenable to suspension culture and high-throughput formats.
The Raji parental cell line, established from a Burkitt??s lymphoma patient, is an Epstein-Barr virus (EBV)-positive, non-adherent suspension culture of B lymphoblastoid origin. Widely employed in immunology and cancer research, Raji cells proliferate robustly and are amenable to genetic manipulation, providing an ideal host for CRISPR/Cas9 engineering. The lymphoblastoid phenotype allows interrogation of oncogenic signaling in a system that complements adherent epithelial models.
FGFR4 encodes a transmembrane tyrosine kinase receptor that is activated by its high-affinity ligands FGF19, FGF21, and FGF23 in conjunction with the co-receptor ??-Klotho and heparan sulfate proteoglycans. Ligand-induced receptor dimerization triggers autophosphorylation and recruitment of the adaptor protein FRS2, which forms a complex with GRB2 and SOS to initiate the RAS?CRAF?CMEK?CERK kinase cascade. Simultaneously, FGFR4 signals through the PI3K?CAKT?CmTOR and PLC?èCPKC pathways, and can activate STAT3 via phosphorylation. These pathways converge on transcription factors such as FOS, JUN, MYC, CCND1, and EGR1, which orchestrate gene expression programs governing proliferation, survival, and differentiation. In hepatocytes, FGFR4 signaling suppresses CYP7A1, the rate-limiting enzyme in bile acid synthesis, by inducing the transcriptional repressor SHP (NR0B2), thereby regulating metabolic homeostasis.
In the Raji B lymphocyte context, disruption of FGFR4 expression creates a clean background to assess FGF-dependent signaling without confounding contributions from other FGFR family members. Although FGFR4 is not a classical oncogenic driver in Burkitt??s lymphoma, examination of downstream mediators offers insight into kinase signaling networks relevant to broader cancer biology. The suspension culture format facilitates scaled experiments such as inhibitor profiling, phospho-flow cytometry, and co-immunoprecipitation of the FGFR4 signalosome. Researchers can exploit this model to investigate crosstalk between FGFR4 pathways and EBV latent gene expression programs or B-cell receptor signaling.
Typical applications include mechanistic dissection of MAPK and PI3K signaling downstream of FGFR4, drug target validation for hepatocellular carcinoma, probing metabolic control of bile acid synthesis, and screening FGFR4 inhibitors. Compatible assays encompass Western blot detection of phosphorylated FGFR4 and effectors (pERK, pAKT), RT-qPCR of target genes (CYP7A1, FOS, MYC), flow cytometry for cell surface FGFR4, and viability/apoptosis analyses (MTS, Annexin V). The polyclonal knockout pool recapitulates genetic heterogeneity, offering a robust platform for compound profiling. For additional technical specifications or to inquire about custom gene-editing services, please contact Ascent Research.
