Mouse somatic mutation orthologous to MELAS A3302G mutation in the mitochondrial tRNA(Leu(UUR)) gene confers respiration defects.

Abstract

We searched for mtDNA harboring somatic mutations in mouse B82 cells, and found an A2748G mutation orthologous to the A3302G mutation in tRNA(Leu(UUR)) gene reported in a patient with MELAS, the most prevalent mitochondrial disease. We isolated subclones of B82 cells until we obtained one subclone harboring >95% A2748G mtDNA. Cytoplasmic transfer of A2748G mtDNA resulted in cotransfer of A2748G mtDNA and respiration defects into mouse ES cells. Thus, A2748G mtDNA is responsible for respiration defects, and the ES cells harboring A2748G mtDNA may be useful for generation of transmitochondrial mice harboring A2748G mtDNA as potential disease models of MELAS.

• Authors: Akinori Shimizu, Shunkei Enoki, Kaori Ishikawa, Takayuki Mito, Kanae Obata, Ruriko Nagashima, Hiromichi Yonekawa, Kazuto Nakada, Jun-Ichi Hayashi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 467 Issue 4 Pg. 1097-102 (Nov 27 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 26381171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• RNA, Transfer
• Leucine

Topics

• Animals
• Leucine (genetics)
• Mice
• Mitochondria (genetics)
• Mutation
• RNA, Transfer (genetics)