Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology

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Szibor , M , Dhandapani , P K , Dufour , E , Holmstrom , K M , Zhuang , Y , Salwig , I , Wittig , I , Heidler , J , Gizatullina , Z , Gainutdinov , T , Fuchs , H , Gailus-Durner , V , de Angelis , M H , Nandania , J , Velagapudi , V , Wietelmann , A , Rustin , P , Gellerich , F N , Jacobs , H T , Braun , T & German Mouse Clinic Consortium 2017 , ' Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology ' , Disease Models & Mechanisms , vol. 10 , no. 2 , pp. 163-171 . https://doi.org/10.1242/dmm.027839

Title: Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology
Author: Szibor, Marten; Dhandapani, Praveen K.; Dufour, Eric; Holmstrom, Kira M.; Zhuang, Yuan; Salwig, Isabelle; Wittig, Ilka; Heidler, Juliana; Gizatullina, Zemfira; Gainutdinov, Timur; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabe; Nandania, Jatin; Velagapudi, Vidya; Wietelmann, Astrid; Rustin, Pierre; Gellerich, Frank N.; Jacobs, Howard T.; Braun, Thomas; German Mouse Clinic Consortium
Other contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute of Biotechnology

Date: 2017-02-01
Language: eng
Number of pages: 9
Belongs to series: Disease Models & Mechanisms
ISSN: 1754-8403
DOI: https://doi.org/10.1242/dmm.027839
URI: http://hdl.handle.net/10138/178992
Abstract: Plants and many lower organisms, but not mammals, express alternative oxidases (AOXs) that branch the mitochondrial respiratory chain, transferring electrons directly from ubiquinol to oxygen without proton pumping. Thus, they maintain electron flow under conditions when the classical respiratory chain is impaired, limiting excess production of oxygen radicals and supporting redox and metabolic homeostasis. AOX from Ciona intestinalis has been used to study and mitigate mitochondrial impairments in mammalian cell lines, Drosophila disease models and, most recently, in the mouse, where multiple lentivector-AOX transgenes conferred substantial expression in specific tissues. Here, we describe a genetically tractable mouse model in which Ciona AOX has been targeted to the Rosa26 locus for ubiquitous expression. The AOX(Rosa26) mouse exhibited only subtle phenotypic effects on respiratory complex formation, oxygen consumption or the global metabolome, and showed an essentially normal physiology. AOX conferred robust resistance to inhibitors of the respiratory chain in organello; moreover, animals exposed to a systemically applied LD50 dose of cyanide did not succumb. The AOX(Rosa26) mouse is a useful tool to investigate respiratory control mechanisms and to decipher mitochondrial disease aetiology in vivo.
Subject: Mitochondria
Mitochondrial disease
Respiratory chain
Alternative oxidase
ALTERNATIVE-OXIDASE
NATIVE ELECTROPHORESIS
PROTEIN COMPLEXES
ACUTE LETHALITY
HUMAN-CELLS
MICE
MITOCHONDRIA
DROSOPHILA
DEFECTS
DEFICIENCY
1182 Biochemistry, cell and molecular biology
3111 Biomedicine
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