title: G7731A mutation in mouse mitochondrial tRNALys regulates late-onset disorders in transmitochondrial mice.
abstract: We previously generated mito-mice-tRNA(Lys7731) as a model for primary prevention of mitochondrial diseases. These mice harbour a G7731A mtDNA mutation in the tRNA(Lys) gene, but express only muscle weakness and short body length by four months. Here, we examined the effects of their aging on metabolic and histologic features. Unlike young mito-mice-tRNA(Lys7731), aged mito-mice-tRNA(Lys7731) developed muscle atrophy, renal failures, and various metabolic abnormalities, such as lactic acidosis and anemia, characteristic of patients with mitochondrial diseases. These observations provide convincing evidence that the respiration defects induced by high G7731A mtDNA levels cause these late-onset disorders that are relevant to mitochondrial diseases.
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mito
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Hashizume
authors.affiliation: Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakada
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan; TARA Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan. Electronic address: jih45@biol.tsukuba.ac.jp.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D017668:Age of Onset; D000375:Aging / Q000235:genetics; D000818:Animals; D004272:DNA, Mitochondrial; D004195:Disease Models, Animal; D008297:Male; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009154:Mutation; D012357:RNA, Transfer, Lys / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D012357:RNA, Transfer, Lys
keywords: G7731A mtDNA mutation; Late-onset disorders; Mitochondrial disease models; Mitochondrial tRNA(Lys) gene; Respiration defects; Transmitochondrial mice