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

Summary.

The organic cation transporter 3 (OCT3), also termed as extraneuronal monoamine transporter (EMT), is known to be expressed in glial cells where it is responsible for the uptake of catecholamines and neurotoxic organic cations such as 1-methyl-4-phenylpyridinium (MPP⁺). We have now analyzed the structure of the human and murine OCT3 gene. The coding regions of both genes consist of 11 exons and 10 introns. All exon-intron junctions contain fully conserved gt/ag consensus splice sites. The human introns are without exception larger than their murine counterparts. In both genes, the introns, apart from intron 1, are located at the same position. Mouse and human exons have the same size with exception of exon 1 which is 15 bp larger in the human gene. The organization of the human OCT3 gene also shows pronounced similarities with other genes of human organic cation transporters such as those 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 investigations of possible polymorphisms and their involvement in e.g. psychiatric disorders; and knowledge of the mouse exon-intron organization is essential for generating a knock-out mouse which should help to recognize the physiological importance of the OCT3.