a mutation in the gene encoding mitochondrial mg2+ channel mrs2 results in demyelination in the rat突变基因编码线粒体mg2 +频道mrs2导致脱髓鞘的老鼠.pdfVIP

A Mutation in the Gene Encoding Mitochondrial Mg2+ Channel MRS2 Results in Demyelination in the Rat 1 2 1,2 2 1 Takashi Kuramoto *, Mitsuru Kuwamura , Satoko Tokuda , Takeshi Izawa , Yoshifumi Nakane , 1,3 4 ´ 5 1 Kazuhiro Kitada , Masaharu Akao , Jean-Louis Guenet , Tadao Serikawa 1 Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 2 Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka, Japan, 3 Laboratory of Mammalian Genetics, Genome Dynamics Research Center, Graduate School of Science, Hokkaido University, Sapporo, Japan, 4 Department of ´ ´ Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 5 Departement de Biologie du Developpement, Institut Pasteur, Paris, France Abstract The rat demyelination (dmy) mutation serves as a unique model system to investigate the maintenance of myelin, because it provokes severe myelin breakdown in the central nervous system (CNS) after normal postnatal completion of myelination. Here, we report the molecular characterization of this mutation and discuss the possible pathomechanisms underlying demyelination. By positional cloning, we found that a G-to-A transition, 177 bp downstream of exon 3 of the Mrs2 (MRS2 magnesium homeostasis factor (Saccharomyces cerevisiae)) gene, generated a novel splice acceptor site which resulted in functional inactivation of the mutant allele. Transgenic rescue with wild-type Mrs2-cDNA validated