Leadership In Controlled Gene Expression

The power and "tightness" of the Tet gene switch is documented by the work of G. Fishman and colleagues (Lee et al. 1998) in which the gene encoding the Diphteria toxin A chain (DTA) was placed under Tet control. Considering that only a few molecules of DTA are sufficient to effectively kill cells, it is an amazing achievement that such transgenic (Tx) animals are viable. When these animals were bred with Tx animals expressing tTA in a cardiac-specific manner, double Tx mouse lines could be established and thrived as long as tTA expression was suppressed by Dox in the drinking water.  Induction of tTA expression by removing Dox from the water supply resulted in DTA production and selective and lethal cardiomyocyte ablation.