title: Mitochondrial reactive oxygen species generation by the SDHC V69E mutation causes low birth weight and neonatal growth retardation.
abstract: We have previously demonstrated that excessive mitochondrial reactive oxygen species caused by mutations in the SDHC subunit of Complex II resulted in premature death in C. elegans and Drosophila, tumors in mouse cells and infertility in transgenic mice. We now report the generation and initial characterization of conditional transgenic mice (Tet-mev-1) using our uniquely developed Tet-On/Off system, which equilibrates transgene expression to endogenous levels. The mice experienced mitochondrial respiratory chain dysfunction that induced reactive oxygen species overproduction. The mitochondrial oxidative stress resulted in excessive apoptosis leading to low birth weight and growth retardation in the neonatal developmental phase in Tet-mev-1 mice.
authors.affiliation: Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ishii
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Akira
authors.initials: A
authors.lastname: Onodera
authors.forename: Kayo
authors.initials: K
authors.lastname: Yasuda
authors.forename: Noboru
authors.initials: N
authors.lastname: Kawabe
authors.forename: Mika
authors.initials: M
authors.lastname: Kirinashizawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Naoki
authors.initials: N
authors.lastname: Maruyama
authors.forename: Philip S
authors.initials: PS
authors.lastname: Hartman
authors.forename: Naoaki
authors.initials: N
authors.lastname: Ishii
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006130:Growth Disorders / Q000209:etiology*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000473:pathology; D009154:Mutation; D041681:NIH 3T3 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology; D019076:Transgenes / Q000235:genetics / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D013385:Succinate Dehydrogenase; D013752:Tetracycline