Insrr Knockout CBRH-7919 Cell Line

The Insrr Knockout CBRH-7919 Cell Line is a CRISPR/Cas9-engineered rat hepatoma cell model in which the Insrr gene has been disrupted to eliminate functional insulin receptor-related receptor expression. This stable in vitro knockout system is generated in the CBRH-7919 background, a hepatocyte-like liver tumor cell line, and is intended for mechanistic studies of receptor tyrosine kinase signaling, extracellular pH sensing, and hepatic signal transduction. The model is suited for experiments requiring defined loss of INSRR activity in a liver-derived cellular context relevant to metabolism and cancer biology.

CBRH-7919 is a rat hepatoma-derived cell line that retains hepatic characteristics and is widely used as an in vitro model for hepatocellular carcinoma-related signaling, liver cell physiology, toxicology, and drug response. Because it combines tumor-associated properties with hepatocyte-like features, this host background is useful for investigating pathways that couple growth control, metabolic regulation, and stress adaptation in liver cells. The line is therefore applicable to studies of hepatic proliferation, survival signaling, and pathway crosstalk under conditions relevant to liver cancer and broader hepatocellular biology.

INSRR is an orphan receptor tyrosine kinase of the insulin receptor family and is activated by alkaline extracellular pH, which promotes receptor dimerization and autophosphorylation. Following activation, INSRR engages adaptor proteins including IRS1, IRS2, SHC1, and GRB2, thereby mediating signaling to the PI3K-AKT and MAPK cascades. Representative downstream pathway components include PIK3CA-PIK3R1, AKT1, MTOR, RPS6KB1, KRAS, BRAF, MAP2K1, and MAPK3, linking INSRR to regulation of cell survival, proliferation, and metabolic responses. In this context, loss of INSRR is expected to reduce alkaline pH-responsive signaling through IRS- and SHC-dependent nodes and to provide a tractable system for studying insulin receptor family pathway specificity alongside related receptors such as INSR and IGF1R.

Within the CBRH-7919 hepatoma background, Insrr knockout provides a relevant model for examining how extracellular acid-base conditions influence hepatic tumor cell signaling and phenotype. This is particularly useful for evaluating pathway dependence under alkaline stress, defining contributions of INSRR to hepatocellular carcinoma-associated signaling networks, and distinguishing INSRR-mediated responses from parallel inputs mediated by INSR or IGF1R. The model can support studies of growth control, survival responses, and metabolic regulation in liver-derived cancer cells.

Applications include western blot-based receptor phosphorylation assays to assess INSRR-dependent phosphotyrosine signaling, phospho-signaling analysis of AKT1, MAPK1/MAPK3, MTOR, or RPS6KB1 after extracellular alkalinization, and RT-qPCR or RNA-seq profiling of transcriptional consequences of Insrr loss. Researchers may also use co-immunoprecipitation to examine altered association of IRS1, IRS2, SHC1, GRB2, or PIK3R1 with insulin receptor family complexes, as well as immunofluorescence and flow cytometry for pathway-state or phenotypic characterization. Functional studies can include proliferation assays, apoptosis assays, metabolic assays, and drug sensitivity studies to evaluate how INSRR disruption modifies hepatic signaling dependencies and therapeutic response. Researchers may contact Ascent Research for additional technical information, product details, or related gene-edited cell models.