Lu K m, Nishimori H, Nakamura Y, Shima K, Kuwajima M
Department of Laboratory Medicine, School of Medicine, Tokushima University, Tokushima, 770-8503, Japan.
Biochem Biophys Res Commun. 1998 Nov 27;252(3):590-4. doi: 10.1006/bbrc.1998.9708.
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.
肉碱是长链脂肪酸线粒体β氧化的必需辅助因子。幼年内脏脂肪变性（JVS）小鼠是全身性肉碱缺乏的动物模型，以常染色体隐性方式遗传。最近，一个编码钠依赖性肉碱协同转运蛋白的人类OCTN2基因被分离出来并定位到人类染色体5q31。由于小鼠jvs基因座被定位到11号染色体上与人染色体5q31同线的区域，我们分离了小鼠octn2基因并在JVS小鼠中筛选其突变。DNA序列分析揭示在octn2第六跨膜结构域内的第352密码子处有一个从CTG（亮氨酸）到CGG（精氨酸）的错义突变。这种氨基酸替换可能导致蛋白质的构象变化，从而导致基因产物功能障碍。因此，我们得出结论，octn2是导致JVS小鼠发病的候选基因。
