The Tet-On Advanced transactivator (also known as rtTA2S-M2) is an alternative version of Tet-On that shows reduced basal expression, and functions at a 10-fold lower Dox concentration than Tet-Off. In addition, its expression is considered to be more stable in eukaryotic cells due to being human codon optimized and utilizing 3 minimal transcriptional activation domains. It was discovered in 2000 as one of two improved mutants by H. Bujard and his colleagues after random mutagenesis of the Tet Repressor part of the transactivator gene