The LBR Knockout Raji Polyclonal Cells are a heterogeneous CRISPR/Cas9-edited cell population derived from the Raji human B-lymphocyte line, engineered for targeted disruption of the LBR gene encoding the lamin B receptor. This polyclonal knockout product provides a physiologically relevant loss-of-function model to investigate LBR-dependent processes in a B-cell lymphoma context. The gene-edited pool enables functional studies of LBR??s dual role in nuclear envelope organization and cholesterol biosynthesis without the selective pressure of monoclonal isolation, preserving population-level heterogeneity that better reflects native cellular diversity. Researchers can probe how LBR ablation impacts nuclear architecture, heterochromatin tethering, and sterol metabolism within Burkitt??s lymphoma-derived B cells, offering a versatile tool for mechanistic and translational studies.
The parental Raji cell line is an Epstein?CBarr virus (EBV)-positive human Burkitt??s lymphoma B-cell line established from an 11-year-old male. Raji cells lack surface immunoglobulin expression but retain key B-cell signaling components, making them a widely used model for B-cell receptor signaling, antigen presentation, and lymphoma biology. Their EBV association and transformed phenotype provide a robust background for examining oncogenic pathways and nuclear-cytoplasmic communication in hematopoietic malignancies. The polyclonal knockout format maintains the inherent genetic and epigenetic characteristics of the parental line while introducing LBR gene disruption, allowing direct comparison with wild-type controls.
LBR is an inner nuclear membrane protein with two distinct functional domains: an N-terminal region that binds lamin B1 and heterochromatin protein 1 (HP1??/??) to tether peripheral heterochromatin, and a C-terminal sterol ??14-reductase domain essential for cholesterol biosynthesis. Through lamin B1 interaction, LBR contributes to nuclear lamina assembly and nuclear envelope stability. Its reduction of the ??14 double bond in sterol intermediates directly impacts cholesterol production, linking nuclear architecture to lipid metabolism. LBR is regulated by Aurora A/B kinases and protein kinase C-mediated phosphorylation, and it interacts with importin ?? for nuclear transport, p53, and barrier-to-autointegration factor (BAF). Downstream effects include modulation of heterochromatin silencing, cholesterol intermediate levels, and nuclear lamina dynamics. In the Raji B-cell context, LBR disruption may alter nuclear morphology, gene expression programs, and metabolic profiles.
In Burkitt??s lymphoma cells, LBR knockout addresses critical gaps in understanding how nuclear envelope dysfunction contributes to B-cell malignancy. Aberrant nuclear morphology is a hallmark of many cancers, and LBR mutations are linked to Pelger-Hu?t anomaly and Greenberg skeletal dysplasia. By eliminating LBR in a transformed B-cell model, researchers can dissect its role in lymphoma cell survival, proliferation, and genomic stability. The cholesterol biosynthesis deficiency resulting from LBR loss makes this model particularly informative for studying metabolic vulnerabilities in lymphoma, as rapidly dividing cancer cells often rely on altered lipid metabolism. Additionally, the interaction with p53 and heterochromatin proteins provides avenues to explore tumor suppressor signaling and epigenetic dysregulation.
This LBR knockout polyclonal cell pool enables diverse applications, including examining nuclear envelope defects using immunofluorescence microscopy, quantifying cholesterol intermediates via biochemical assays, and profiling transcriptomic changes by RNA-seq. Researchers can perform drug sensitivity screens for sterol biosynthesis inhibitors or apoptosis assays by flow cytometry to assess therapeutic responses. The product is suitable for mechanistic studies of lamin B1?Cdependent nuclear organization, HP1-mediated gene silencing, and B-cell receptor signaling in the absence of LBR. Further validation may include Western blotting to confirm loss of LBR protein and RT-qPCR for downstream target analysis. For technical inquiries or custom projects, please contact Ascent Research.
