Mutation of carnitine transporter OCTN2 in primary systemic carintine deficient jvs mice

• Published in: Japanese Journal of Pharmacology 1999, Vol.79 (suppl.1), p.108-108
• Main Authors: Tamai, Ikumi, Ohashi, Rikiya, Nezu, Junichi, Oku, Asuka, Hashimoto, Noriyoshi, Nikaido, Hiroko, Sai, Yoshimichi, Hayakawa, Jun-ichiro, Shimane, Miyuki, Tsuji, Akira
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)34455-5

Carnitine deficiency leads to diseases in heart and muscle in patients and in its murine model, jvs. A defect of carnitine transporters has been thought to be a cause for the primary systemic carnitine deficiency. We have recently identified membrane transporter family OCTNs from human as a carnitine transporter. In the present study, we isolated its mouse counterpart and analyzed carnitine transport characteristics. Mouse OCTN2 encoded 557 amino acids with 85% identity with human OCTN2 and is expressed strongly in kidney. Carnitine transport by mouse OCTN2 was sodium ion dependent, saturable and inhibited by carnitine analogues. In jvs mice, a single nucleotide transition leading to substitution of leucine (CTG) at codon 352 with arginine (CGG) was identified. Furthermore, the mutant OCTN2 did not exhibit any carnitine transport activity, although similar levels of protein were detected in the transfected cells. These results demonstrate that mouse OCTN2 has a physiologically important role in carnitine transport and its genetic functional defect will lead to the primary systemic carnitine deficiency in mice.