A gene expression modulation system comprising a gene expression cassette that is capable of being expressed in a host cell. The cassette comprises a polynucleotide that encodes a polypeptide that comprises: (i) a transactivation domain; (ii) a DNA-binding domain that recognizes a response element associated with a gene whose expression is to be modulated; and (iii) a Group H nuclear receptor ligand binding domain that comprising a mutation of SEQ ID NO: 1 selected from T52P, F109L, M125P, M125R, M125L, M125C and M125W. The SEQ ID NO: 1 is the insect ecdysone receptor (EcR) from the spruce budworm Choristoneura fumiferana (CfEcR). The mutations exhibit increased activity in response to tetrahydraquinoline ligands.