Analysis of mouse models of cytochrome c oxidase deficiency owing to mutations in COX6A1

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08327
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Tohoku University
• Principal Investigator: Makino Satoshi 東北大学, 東北メディカル・メガバンク機構, 助教 (30423403)
• Co-Investigator(Kenkyū-buntansha): 田宮 元 東北大学, 東北メディカル・メガバンク機構, 教授 (10317745) ; 遠山 育夫 滋賀医科大学, 神経難病研究センター, 教授 (20207533)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 人類遺伝学 / ミトコンドリア / 末梢神経

Outline of Final Research Achievements

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Whole-genome sequencing study in the probands, followed by mutation screening in the two families, revealed a disease-specific 5-bp deletion in a splicing element of intron 2 adjacent to the 3rd exon of COX6A1. Cox6a1 null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. On the other hand, by electron microscope, no special findings were observed in nerve fibers. Therefore, we focused on the mitochondrial ferritin (FtMt) of metal binding protein present in mitochondria. Under oxidative stress conditions induced by hydrogen peroxide, the expression of FtMt were increased. This finding suggests that FtMt protects cells against oxidative stress by hydrogen peroxide.

Free Research Field

分子生物学