This human RAR-related orphan receptor gamma (ROR(gamma)) mRNA is expressed from the RORC gene in two forms via alternate usage of tissue-specific promoters. Variant 1 mRNA is expressed in numerous tissues, and encodes receptor isoform 1, referred to as ROR(gamma). Variant 2 mRNA comprises an alternate exon 1 that replaces the exon 1 and 2 sequences found in the Variant 1 transcript. Consequently, variant 2 mRNA presents a unique 5'UTR and modified N-terminal ORF sequences, resulting in the expression of a shorter isoform 2 receptor. The isoform 2 receptor is expressed predominantly in specialized immune cells developing within the thymus; as such it is referred to as ROR(gamma)t. This nuclear receptor assay system utilizes proprietary human cells engineered to provide high-level expression of a hybrid form of the human RAR-related orphan receptor gamma. The N-terminal DNA binding domains (DBD) of the native ROR(gamma) and ROR(gamma)t receptors have been substituted with that of the yeast GAL4-DBD. Hence, the GAL4- ROR(gamma) hybrid receptor expressed in these reporter cells will not discern any functional differences that may exist between the native isoform 1 and isoform 2 receptors. As is true in vivo, uncharacterized molecular activators present in these reporter cells maintain ROR(gamma) in a constant state of high-level activity. The principal application of this reporter assay system is in the screening of test samples to quantify inverse-agonist activities that they may exert against human ROR(gamma). Reporter cells are prepared using INDIGO
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