title: A missense mutation of mouse OCTN2, a sodium-dependent carnitine cotransporter, in the juvenile visceral steatosis mouse.
abstract: Carnitine is an essential cofactor for the mitochondrial beta-oxidation of long-chain fatty acids. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, is inherited in an autosomal recessive manner. Recently, a human OCTN2 gene encoding a sodium-dependent carnitine cotransporter was isolated and mapped to human chromosome 5q31. Since the mouse jvs locus was assigned to the region of chromosome 11 where it is syntenic to human chromosome 5q31, we isolated the mouse octn2 gene and screened for its mutation in the jvs mouse. DNA sequencing analysis disclosed a missense mutation from CTG (Leu) to CGG (Arg) at codon 352 located within the sixth transmembrane domain of octn2. This amino acid replacement possibly causes the conformational change of the protein that leads to dysfunction of the gene product. Hence, we conclude that octn2 is a candidate gene responsible for the JVS mouse.
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Tokushima University, Tokushima, 770-8503, Japan.
authors.forename: K m
authors.initials: Km
authors.lastname: Lu
authors.forename: H
authors.initials: H
authors.lastname: Nishimori
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Shima
authors.forename: M
authors.initials: M
authors.lastname: Kuwajima
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002331:Carnitine / Q000172:deficiency*; D002352:Carrier Proteins / Q000235:genetics*; D018076:DNA, Complementary / Q000737:chemistry; D004195:Disease Models, Animal; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D027701:Organic Cation Transport Proteins; D010641:Phenotype; D016415:Sequence Alignment; D000074058:Solute Carrier Family 22 Member 5; D014804:Vitamin B Deficiency / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine