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Genomic Structure and in Vivo Expression of the Human Organic Anion Transporter 1 (hOAT1) Gene

https://doi.org/10.1006/bbrc.2000.3230Get rights and content

Abstract

The human organic anion transporter 1 (hOAT1) plays a key role in the secretion of an array of potentially toxic organic anions including many clinically important drugs. Here we report on the genomic cloning of hOAT1. A human genomic library was used for screening of a PAC (P1 artificial chromosome) clone applying PCR techniques. Sequencing of several restriction subclones and of a PCR-generated clone revealed that the hOAT1 gene spans 8.2 kb and is composed of 10 exons divided by 9 introns. RT-PCR studies in a human kidney 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 hybridization (FISH) we mapped the hOAT1 gene as a single signal to chromosome 11q13.1-q13.2. Additionally, 600 bp of the 5′ flanking region was analyzed, illustrating the probable transcription start site at nt −280, a NF-κB-site at nt −397 and several putative transcription factor binding sites.

References (35)

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The nucleotide sequences reported in this paper have been submitted to EMBL/GenBank with Accession Nos. AJ249369 (OAT1 gene), AJ251529 (isoform hOAT1-3), and AJ271205 (isoform hOAT1-4).

1

These authors contributed equally to this study.

2

To whom correspondence should be addressed. Fax: +49-551-395883. E-mail: [email protected].

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