An In-Vitro Cell System Useful For Identification of RORgamma Antagonists

The retinoid-related orphan receptors alpha, beta and gamma (RORalpha, beta and gamma , also referred to as NR1F1, 2 and 3, respectively) comprise a distinct subfamily of nuclear receptors. Study of ROR-deficient mice has implicated RORs in the regulation of a number of biological processes and revealed potential roles for these proteins in several pathologies. NIH investigators have developed an in-vitro system using CHO cells stably expressing a TET-On expression vector regulating RORgamma and a RORE-Luciferase reporter. This system allows inducible expression of RORgamma upon addition of doxycycline. Upon its induction RORgamma binds to the RORE in the luciferase reporter plasmid and induces luciferase. This system can be used to identify RORgamma antagonists. This system has been tested successfully in 1536-well plate high throughput analysis.