MTNR1A Knockout Cell Line (HEK293)

The choice depends on whether you are studying MTNR1A (MT1, melatonin receptor type 1A)'s role as a Gi-coupled melatonin receptor or its functions in circadian rhythm regulation and sleep biology. The Knockout line is the standard tool for asking whether MT1 is required for melatonin-induced signaling — MT1 is a seven-transmembrane GPCR that, with MT2 (MTNR1B), mediates melatonin's circadian and sleep-promoting effects through Gi-coupled cAMP suppression and other downstream signaling. Overexpression is useful for studying MT1 in heterologous expression contexts. For circadian rhythm and sleep research, the EDITGENE MTNR1A Knockout in HEK293 is a mechanistic platform — HEK293 supports systematic structure-function studies of MT1. MTNR1B (MT2) paralog expression analysis is essential given partial functional overlap. Rescue with wild-type or signaling-deficient MT1 is the standard specificity control. The knockout is a critical specificity tool for ramelteon (FDA-approved MT1/MT2 agonist for insomnia), agomelatine (depression/MT receptors), tasimelteon (non-24-hour sleep-wake disorder), and emerging melatonin receptor modulators.

Primary applications: • Melatonin-induced signaling: cAMP suppression following melatonin stimulation (Gi-coupled receptor signaling) to characterize MT1-dependent signaling. • Ramelteon specificity: critical genetic control for ramelteon (Rozerem) — the FDA-approved MT1/MT2 agonist for chronic insomnia. • Agomelatine and tasimelteon studies: assessment of these melatonin receptor modulators in MT1-null background. • MTNR1A polymorphism studies: rescue with disease-associated MTNR1A polymorphisms for pharmacogenomic studies. EDITGENE recommends this model for researchers investigating melatonin receptor biology, circadian rhythm pharmacology, and sleep disorder therapeutic development.

Yes. MT1 rescue experiments are well-established for GPCR pharmacology research: • Construct design: use a codon-modified MTNR1A sequence with a small intracellular C-terminal tag (FLAG, HA). MT1 is a seven-transmembrane GPCR — preserve extracellular ligand-binding pocket. • Signaling-deficient rescue: DRY motif mutations or specific intracellular loop mutations disrupt Gi-coupling. • Surface localization validation: confirm plasma membrane localization by cell surface staining. • Functional readout: rescue should restore melatonin-induced cAMP suppression (Gi signaling) and ramelteon responsiveness. HEK293 transduces efficiently with lentivirus and supports stable rescue line generation.