In Stock Cell Lines
The Mlh1 Knockout LLC Cell Line is a CRISPR/Cas9-edited mouse Lewis lung carcinoma (LLC) line with targeted disruption of the DNA mismatch repair gene Mlh1. Loss of MLH1 abolishes MutL?? complex formation with PMS2, leading to microsatellite instability and accumulation of mutations, while impairing interactions with PCNA and downstream DNA repair effectors. This model is well-suited for studying MMR-deficient lung cancer, Lynch syndrome, and MSI-H tumors in an immunocompetent syngeneic background. Applications span investigation of DNA repair pathways, drug sensitivity/resistance screening, and immunotherapy response evaluation using assays such as MSI fragment analysis, caspase-3/7 apoptosis assays, and in vivo xenograft studies.
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The Mlh1 Knockout LLC Cell Line is a CRISPR/Cas9-edited knockout cell line derived from mouse Lewis lung carcinoma (LLC) cells. Using CRISPR/Cas9-mediated gene disruption, the locus encoding MLH1??a central component of the DNA mismatch repair (MMR) machinery??has been targeted to create a stable loss-of-function model. This cell line provides a genetically defined tool for dissecting MMR deficiency in a well-characterized murine lung cancer background, enabling detailed mechanistic and translational studies without the confounds of heterologous systems.
LLC cells originate from a spontaneous lung carcinoma that arose in a C57BL/6 mouse, a strain widely employed for syngeneic tumor models. As a classic non-small cell lung cancer line, LLC recapitulates key features of aggressive tumor growth and metastatic dissemination when implanted subcutaneously, intravenously, or orthotopically. Their syngeneic nature on the C57BL/6 background permits interrogation of tumor?Chost immune interactions in an immunocompetent setting, making them especially suitable for evaluating immunotherapies.
The MLH1 protein partners with PMS2 to form the MutL?? heterodimer, which recognizes base?Cbase mismatches and insertion/deletion loops generated during DNA replication. MutL?? interacts with PCNA, EXO1, and other MMR components such as MSH2 and MSH6 to coordinate strand-specific excision and resynthesis. Loss of MLH1 abrogates this repair pathway, resulting in microsatellite instability (MSI) and a hypermutator phenotype. Downstream, the persistent DNA damage activates caspase-3 and PARP, driving apoptosis, while upstream regulators including DNA damage signals and promoter hypermethylation can modulate MLH1 expression. The knockout therefore disrupts a network involving PMS2, EXO1, PCNA, and DNA polymerases, with consequences for genomic integrity and chemosensitivity.
In the LLC context, Mlh1 knockout generates a lung carcinoma model that mirrors the biology of MMR-deficient malignancies such as Lynch syndrome-associated and MSI-H solid tumors. The murine origin and immunocompetent host compatibility allow researchers to investigate how a defective MMR pathway influences tumor mutational burden and immune surveillance, as well as the efficacy of checkpoint inhibitors (e.g., anti-PD-1). This model is particularly valuable for examining the interplay between DNA repair status and the tumor microenvironment in lung cancer.
Researchers can utilize the Mlh1 Knockout LLC Cell Line for a broad spectrum of functional studies, including dissection of MMR mechanisms, drug sensitivity/resistance profiling with agents like cisplatin and 5-fluorouracil, and apoptosis signaling analyses. Representative assays include Western blotting for MLH1 and PMS2 to verify knockout, MSI testing by fragment analysis, in vitro mismatch repair functional assays, cell viability and caspase-3/7 activation assays, immunofluorescence for ??H2AX foci, and syngeneic xenograft tumor growth experiments. For additional information, please contact Ascent Research.
