A missense mutation of mouse OCTN2, a sodium-dependent carnitine cotransporter, in the juvenile visceral steatosis mouse

Carnitine is an essential cofactor for the mitochondrial beta-oxidation of long-chain fatty acids. The juvenile visceral steatosis (JVS) mouse, an ani mal model of systemic carnitine deficiency, is inherited in an autosomal re cessive manner. Recently, a human OCTN2 gene encoding a sodium-dependent ca rnitine cotransporter was isolated and mapped to human chromosome 5q31. Sin ce 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 disclo sed a missense mutation from CTG (Leu) to CGG (Arg) at codon 352 located wi thin the sixth transmembrane domain of octn2. This amino acid replacement p ossibly causes the conformational change of the protein that leads to dysfu nction of the gene product. Hence, we conclude that octn2 is a candidate ge ne responsible for the JVS mouse. (C) 1998 Academic Press.