TY  - JOUR
A1  - Szibor, Marten
A1  - Dhandapani, Praveen K.
A1  - Dufour, Eric
A1  - Holmström, Kira Margareta
A1  - Zhuang, Yuan
A1  - Salwig, Isabelle
A1  - Wittig, Ilka
A1  - Heidler, Juliana
A1  - Gizatullina, Zemfira
A1  - Gainutdinov, Timur
A1  - Fuchs, Helmut
A1  - Gailus-Durner, Valérie
A1  - Hrabé de Angelis, Martin
A1  - Nandania, Jatin
A1  - Velagapudi, Vidya
A1  - Wietelmann, Astrid
A1  - Rustin, Pierre
A1  - Gellerich, Frank Norbert
A1  - Jacobs, Howard T.
A1  - Braun, Thomas
T1  - Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology
T2  - Disease models & mechanisms
N2  - 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 AOXRosa26 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 AOXRosa26 mouse is a useful tool to investigate respiratory control mechanisms and to decipher mitochondrial disease aetiology in vivo.
KW  - Mitochondria
KW  - Mitochondrial disease
KW  - Respiratory chain
KW  - Alternative oxidase
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43241
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-432410
SN  - 1754-8411
SN  - 1754-8403
N1  - This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
VL  - 10
IS  - 2
SP  - 163
EP  - 171
PB  - Company of Biologists Limited
CY  - Cambridge
ER  -