The MLH1 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphocyte cell line, designed to disrupt the MLH1 gene. This gene-edited product provides a heterogeneous pool of cells carrying targeted disruptions in MLH1, enabling loss-of-function studies without clonal isolation. Serving as a genetically defined model for DNA mismatch repair (MMR) deficiency, the polyclonal format preserves biological variability and facilitates robust experimental comparisons against wild-type or control populations. This knockout model is intended for use in a broad spectrum of functional genomics studies, drug response profiling, and mechanistic investigations of genomic instability.
The parental Raji cell line is an EBV-positive B lymphocyte line derived from Burkitt’s lymphoma. As a suspension hematopoietic model, Raji cells display B-cell features like immunoglobulin expression and are used in immunology and oncology to study humoral immunity, lymphomagenesis, and viral oncogenesis. The EBV background enables exploration of interactions between viral latency and DNA repair pathways.
The MLH1 gene encodes a core component of the MutL?? heterodimer, partnering with PMS2 to coordinate post-replicative MMR. Upon mismatch recognition by MutS?? (MSH2-MSH6) or MutS??, MLH1-PMS2 is recruited and directs Exonuclease 1 (EXO1)-mediated excision, PCNA-dependent resynthesis, and ligation. MLH1 also associates with PMS1 and MLH3. Its transcription is controlled by E2F1 and TP53, while epigenetic silencing via promoter hypermethylation commonly inactivates MLH1 in cancers. MLH1 loss abolishes MMR, causing microsatellite instability and elevated mutation rates.
In the Raji B-cell context, MLH1 knockout generates a MMR-deficient model for investigating hematopoietic malignancies and Lynch syndrome-associated tumors. This system facilitates studies on how MMR loss drives lymphomagenesis and how B-cell-specific processes such as somatic hypermutation interface with MMR status. It can be used to probe MSI-driven oncogenesis in lymphoid cells and synthetic lethalities or drug sensitivities stemming from MMR deficiency.
Researchers can use these polyclonal knockout cells for microsatellite instability assays, mutation frequency analysis, and cell viability screening with DNA-damaging agents like temozolomide. They are suitable for immune checkpoint inhibitor response studies due to MSI-driven immunogenicity. Standard techniques??western blotting, RT-qPCR, flow cytometry, and immunofluorescence??enable detailed characterization of MLH1 expression and MMR activity. For additional information or a quote, contact Ascent Research.
