Genomic structure and in vivo expression of the human organic anion transporter 1 (hOAT1) gene

The human organic anion transporter 1 (hOAT1) plays a key role in the secre tion of an array of potentially toxic organic anions including many clinica lly important drugs. Here we report on the genomic cloning of hOAT1. A huma n genomic library was used for screening of a PAC (P1 artificial chromosome ) clone applying PCR techniques. Sequencing of several restriction subclone s and of a PCR-generated clone revealed that the hOAT1 gene spans 8.2 kb an d is composed of 10 exons divided by 9 introns. RT-PCR studies in a human k idney specimen led to the detection of two new splice variants, hOAT1-3 and hOAT1-4, showing a 132-bp in-frame deletion. Using fluorescence in situ hy bridization (FISH) we mapped the hOAT1 gene as a single signal to chromosom e 11q13.1-q13.2. Additionally, 600 bp of the 5' flanking region was analyze d, illustrating the probable transcription start site at nt -280, a NF-kapp a B-site at nt -397 and several putative transcription factor binding sites . (C) 2000 Academic Press.