In response to exposure to hypertonic environment, cells accumulate small organic solutes termed osmolytes that protect them from the adverse effects of hypertonicity. Some osmolytes (myo-inositol, betaine and taurine) are accumulated by specific transporters. Those transporters have been cloned by expression cloning techniques. Transcription of osmolyte transporters is induced by hypertonicity. In situ hybridization reveals the localization of the Na+/myo-inositol cotransporter and the betaine transporter (BGT1) mRNAs in the kidney. The BGT1 gene was cloned and its 5' flanking region has been characterized A 13 bp tonicity responsive enhancer (TONE) has been identified. Analysis of transgenic mice harboring a 5' flanking region of the BGT1 gene, that included TONE, showed that it provides inducible reporter expression in kidney medulla.