Molecular and functional characterization of organic cation/carnitine transporter family in mice

Carnitine is essential for beta -oxidation of fatty acids, and a defect of cell membrane transport of carnitine leads to fatal systemic carnitine defi ciency. We have already shown that a defect of the organic cation/carnitine transporter OCTN2 is a primary cause of systemic carnitine deficiency. In the present study, we further isolated and characterized new members of the OCTN family, OCTN1 and -3, in mice. All three members were expressed commo nly in kidney, and OCTN1 and -2 were also expressed in various tissues, whe reas OCTN3 was characterized by predominant expression in testis. When thei r cDNAs were transfected into HEK293 cells, the cells exhibited transport a ctivity for carnitine and/or the organic cation tetraethylammonium (TEA). C arnitine transport by OCTN1 and OCTN2 was Na+-dependent, whereas that by OC TN3 was Na+-independent. TEA was transported by OCTN1 and OCTN2 but not by OCTN3. The relative uptake activity ratios of carnitine to TEA were 1.78, 1 1.3, and 746 for OCTN1, -2, and -3, respectively, suggesting high specifici ty of OCTN3 for carnitine and significantly lower carnitine transport activ ity of OCTN1. Thus, OCTN3 is unique in its limited tissue distribution and Na+-independent carnitine transport, whereas OCTN1 efficiently transported TEA with minimal expression of carnitine transport activity and may have a different role from other members of the OCTN family.