Analysis of the gene structure of the human (SLC22A3) and murine (Slc22a3)extraneuronal monoamine transporter

The organic cation transporter 3 (OCT3), also termed as extraneuronal monoa mine transporter (EMT), is known to be expressed in glial cells where it is responsible for the uptake of catecholamines and neurotoxic organic cation s such as 1-methyl-4-phenylpyridinium (MPP+). We have now analyzed the stru cture of the human and murine OCT3 gene. The coding regions of both genes c onsist of 11 exons and 10 introns. All exon-intron junctions contain fully conserved gt/ag consensus splice sites. The human introns are without excep tion larger than their murine counterparts. In both genes, the introns, apa rt from intron 1, are located at the same position. Mouse and human exons h ave the same size with exception of exon 1 which is 15 bp larger in the hum an gene. The organization of the human OCT3 gene also shows pronounced simi larities with other genes of human organic cation transporters such as thos e for hOCT1, hOCTN2, hORCTL3, and hORCTL4. The genes of these transporters share about the same exon-intron structure and exon sizes, indicating that the genes may have evolved from a common anchestor gene through duplication . Knowledge of the human gene structure of the OCT3 should enable investiga tions of possible polymorphisms and their involvement in e.g. psychiatric d isorders; and knowledge of the mouse exon-intron organization is essential for generating a knock-out mouse which should help to recognize the physiol ogical importance of the OCT3.