OSMOLARITY IN RENAL MEDULLA OF TRANSGENIC MICE REGULATES TRANSCRIPTION VIA 5'-FLANKING REGION OF CANINE BGT1 GENE

Betaine is a major compatible osmolyte accumulated in the mammalian ki dney medulla and in Madin-Darby canine kidney cells in response to hyp er tonicity, The accumulation is the result of an increase in maximal velocity of the Na+- and Cl--coupled betaine transporter designated BG T1. me have previously cloned the canine BGT1 gene and identified a to nicity-responsive enhancer element (TonE) in its 5'-flanking region. H ere we report studies of transgenic mice that have in their genome 2.4 kb of the 5'-flanking region of the canine BGT1 gene in front of a ch loramphenicol acetyltransferase (CAT) reporter. Expression of CAT mRNA was detected only in the renal medulla and was increased by experimen tal manipulations that increase the tonicity of the renal medulla and decreased by manipulations that decrease medullary tonicity. We conclu de that the 2.4-kb 5'-flanking region of the BGT1 gene mediates an inc rease in transcription in response to hyperosmolarity in the renal med ulla.