Mutations of OCTN2, an organic cation/carnitine transporter lead to deficient cellular carnitine uptake in primary carnitine deficiency

Human Molecular Genetics

Volumn 8, Issue 4, 1999, Pages 655-660

  Tang, Nelson L S ^a   Ganapathy, V ^b   Wu, Xiang ^b   Hui, Joannie ^a   Seth, Pankaj ^b   Yuen, Patrick M P ^a   Fok, T F ^a   Hjelm, N M ^a  

^a CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^b MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARNITINE; CARRIER PROTEIN; CATION; COMPLEMENTARY DNA;

AMINO ACID TRANSPORT; ARTICLE; CARNITINE DEFICIENCY; CONTROLLED STUDY; DNA POLYMORPHISM; FAMILY STUDY; FEMALE; GENE MUTATION; HUMAN; HUMAN CELL; ION TRANSPORT; MALE; MISSENSE MUTATION; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; STOP CODON;

EID: 0032997735     PISSN: 09646906     EISSN: None     Source Type: Journal    
DOI: 10.1093/hmg/8.4.655     Document Type: Article

References (24)

1. Engel, A.G., Rebouche, C.J., Wilson, D.M., Glasgow, A.M., Romshe, C.A. and Cruse, R.P. (1981) Primary systemic carnitine deficiency. II. Renal handling of carnitine. Neurology, 31, 819-825.
2. Karpati, G., Carpenter, S., Engel, A.G., Watters, G., Allen, J., Rothman, S., Klassen, G. and Mamer, O.A. (1975) The syndrome of systemic carnitine deficiency. Clinical, morphologic, biochemical and pathophysiologic features. Neurology, 25, 16-24.
3. Stanley, C.A., DeLeeuw, S., Coates, P.M., Vianey-Liaud, C., Divry, P., Bonnefont, J.P., Saudubray, J.M., Haymond, M., Trefz, F.K., Breningstall, G.N., Wappner, R.S., Byrd, D.J., Sansaricq, C., Tein, I., Grover, W., Valle, D., Rutledge, S.L. and Treem, W.R. (1991) Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake. Ann. Neurol., 30, 709-716.
4. Treem, W.R., Stanley, C.A., Finegold, D.N., Hale, D.E. and Coates, P.M. (1988) Primary carnitine deficiency due to a failure of carnitine transport in kidney, muscle and fibroblasts. New Engl. J. Med., 319, 1331-1336.
5. Tein, I., Bukovac, S.W. and Xie, Z.W. (1996) Characterization of the human plasmalemmal carnitine transporter in cultured skin fibroblasts. Arch. Biochem. Biophys., 329, 145-155.
6. Prasad, P.D., Huang, W., Ramamoorthy, S., Carter, A.L., Leibach, F.H. and Ganapathy, V. (1996) Sodium-dependent carnitine transport in human placental choriocarcinoma cells. Biochim. Biophys. Acta, 1284, 109-117.
7. Roque, A.S., Prasad, P.D., Bhatia, J.S., Leibach, F.H. and Ganapathy, V. (1996) Sodium-dependent high-affinity binding of carnitine to human placental brush border membranes. Biochim. Biophys. Acta, 1282, 274-282.
8. Horiuchi, M., Kobayashi, K., Yamaguchi, S., Shimizu, N., Koizumi, T., Nikaido, H., Hayakawa, J., Kuwajima, M. and Saheki, T. (1994) Primary defect of juvenile visceral steatosis (jvs) mouse with systemic carnitine deficiency is probably in renal carnitine transport system. Biochim. Biophys. Acta. 1226, 25-30.
9. Nikaido, H., Horiuchi, M., Hashimoto, N., Saheki, T. and Hayakawa, J. (1995) Mapping of jvs (juvenile visceral steatosis) gene, which causes systemic carnitine deficiency in mice, on chromosome 11. Mamm. Genome, 6, 369-370.
10. Shoji, Y., Koizumi, A., Kayo, T., Ohata, T., Takahashi, T., Harada, K. and Takada, G. (1998) Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q. Am. J. Hum. Genet., 63, 101-108.
11. Wu, X., Prasad, P.D., Leibach, F.H. and Ganapathy, V. (1998) cDNA sequence, transport function and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem. Biophys. Res. Commun., 246, 589-595.
12. Tamai, I., Ohashi, R., Nezu, J., Yabuuchi, H., Oku, A., Shimane, M., Sai, Y. and Tsuji, A. (1998) Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J. Biol. Chem., 273, 20378-20382.
13. Tang, N.L., Hui, J., Law, L.K., To, K.F., Ruiter, J.P., IJIst, L., Wanders, R.J., Ho, C.S., Fok, T.F., Yuen, P.M. and Hjelm, N.M. (1998) Primary plasmalemmal carnitine transporter defect manifested with dicarboxylic aciduria and impaired fatty acid oxidation. J. Inherit. Metab. Dis., 21, 423-425.
14. Rebouche, C.J., Lombard, K.A. and Chenard, C.A. (1993) Renal adaptation to dietary carnitine in humans. Am. J. Clin. Nutr., 58, 660-665.
15. Koepsell, H. (1998) Organic cation transporters in intestine, kidney, liver and brain. Annu. Rev. Physiol., 60, 243-266.
16. Grundemann, D., Gorboulev, V., Gambaryan, S., Veyhl, M. and Koepsell, H. (1994) Drug excretion mediated by a new prototype of polyspecific transporter. Nature, 372, 549-552.
17. Okuda, M., Saito, H., Urakami, Y., Takano, M. and Inui, K. (1996) cDNA cloning and functional expression of a novel rat kidney organic cation transporter. OCT2. Biochem. Biophys. Res. Commun., 224, 500-507.
18. Kekuda, R., Prasad, P.D., Wu, X., Wang, H., Fei, Y.J., Leibach, F.H. and Ganapathy, V. (1998) Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J. Biol. Chem., 273, 15971-15979.
19. Tamai, I., Yabuuchi, H., Nezu, J., Sai, Y., Oku, A., Shimane, M. and Tsuji, A. (1997) Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. FEBS Lett., 419, 107-111.
20. Schoemig, E., Spitzenberger, F., Engelhardt, M., Martel, F., Oerding, N. and Gruendemann, D. (1998) Molecular cloning and characterization of two novel transport proteins from rat kidney. FEBS Lett., 425, 79-86.
21. Garavaglia, B., Uziel, G., Dworzak, F., Carrara, F. and DiDonato, S. (1991) Primary carnitine deficiency: heterozygote and intrafamilial phenotypic variation. Neurology, 41, 1691-1693.
22. Nelson, M. and McClelland, M. (1992) Use of DNA methyltransferase/endonuclease enzyme combinations for megabase mapping of chromosomes. Methods Enzymol., 216, 279-303.
23. Blakely, R.D., Clark, J.A., Rudnick, G. and Amara, S.G. (1991) Vaccinia-T7 RNA polymerase expression system: evaluation for the expression cloning of plasma membrane transporters. Anal. Biochem., 194, 302-308.
24. 0. Am. J. Physiol., 272, G1463-G1472.