G7731A mutation in mouse mitochondrial tRNALys regulates late-onset disorders in transmitochondrial mice

Akinori Shimizu; Takayuki Mito; Osamu Hashizume; Hiromichi Yonekawa; Kaori Ishikawa; Kazuto Nakada; Jun-Ichi Hayashi

doi:10.1016/j.bbrc.2015.02.070

G7731A mutation in mouse mitochondrial tRNALys regulates late-onset disorders in transmitochondrial mice

Biochem Biophys Res Commun. 2015 Mar 27;459(1):66-70. doi: 10.1016/j.bbrc.2015.02.070. Epub 2015 Feb 23.

Authors

Akinori Shimizu¹, Takayuki Mito¹, Osamu Hashizume¹, Hiromichi Yonekawa², Kaori Ishikawa¹, Kazuto Nakada³, Jun-Ichi Hayashi⁴

Affiliations

¹ Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan.
² Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
³ 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.
⁴ 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.

PMID: 25721669
DOI: 10.1016/j.bbrc.2015.02.070

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.

Keywords: G7731A mtDNA mutation; Late-onset disorders; Mitochondrial disease models; Mitochondrial tRNA(Lys) gene; Respiration defects; Transmitochondrial mice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age of Onset
Aging / genetics
Animals
DNA, Mitochondrial
Disease Models, Animal
Male
Mice, Inbred Strains
Mice, Mutant Strains
Mitochondrial Diseases / genetics*
Mitochondrial Diseases / metabolism
Mitochondrial Diseases / mortality
Mitochondrial Diseases / pathology
Mutation*
RNA, Transfer, Lys / genetics*

Substances

DNA, Mitochondrial
RNA, Transfer, Lys