MOLECULAR-CLONING AND CHARACTERIZATION OF NKT, A GENE-PRODUCT RELATEDTO THE ORGANIC CATION TRANSPORTER FAMILY THAT IS ALMOST EXCLUSIVELY EXPRESSED IN THE KIDNEY

We have identified a gene product (NKT) encoding an apparently novel t ranscript that appears to be related to the organic ion transporter fa mily and is expressed al most exclusively in the kidney, Analysis of t he deduced 546-amino acid protein sequence indicates that NKT is a uni que gene product which shares a similar transmembrane domain hydropath y profile as well as transporter-specific amino acid motifs with a var iety of bacterial and mammalian nutrient transporters, Nevertheless, t he overall homology of NKT to two recently cloned organic ion transpor t proteins (NLT and OCT-1) is significantly greater; together these th ree gene products may represent a new subgroup of transporters, The NK T was characterized further with respect to its tissue distribution an d its expression during kidney development. A 2.5-kilobase transcript was found in kidney and at much lower levels in brain, but not in a nu mber of other tissues, Studies on the embryonic kidney indicate that t he NKT transcript is developmentally regulated with significant expres sion beginning at mouse gestational day 18 and rising just before birt h, consistent with a role in differentiated kidney function, Moreover, in situ hybridization detected specific signals in mouse renal proxim al tubules. NKT was mapped by linkage disequilibrium to mouse chromoso me 19, the same site to which several mouse mutations localize, includ ing that for osteochondrodystrophy (ocd). Although initial experiments in a Xenopus oocyte expression system failed to demonstrate transport of known substrates for OCT-1, the homology to OCT-1 and other transp orters, along with the proximal tubule localization, raise the possibi lity that this gene may play a role in organic solute transport or dru g elimination by the kidney.