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Szibor, M.* ; Dhandapani, P.K.* ; Dufour, E.* ; Holmström, K.M.* ; Zhuang, Y.* ; Salwig, I.* ; Wittig, I.* ; Heidler, J.* ; Gizatullina, Z.* ; Gainutdinov, T.* ; German Mouse Clinic Consortium (Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Aguilar-Pimentel, J.A. ; Schmidt-Weber, C.B. ; Becker, L. ; Adler, T. ; Treise, I. ; Horsch, M. ; Beckers, J. ; Moreth, K. ; Garrett, L. ; Hölter, S.M. ; Zimprich, A. ; Wurst, W. ; Hans, W. ; Amarie, O.V. ; Graw, J. ; Rozman, J. ; Calzada-Wack, J. ; Da Silva-Buttkus, P. ; Neff, F. ; Rácz, I. ; Rathkolb, B. ; Östereicher, M.A. ; Steinkamp, R. ; Lengger, C. ; Maier, H. ; Stoeger, C. ; Leuchtenberger, S.) ; Nandania, J.* ; Velagapudi,V.* ; Wietelmann, A.* ; Rustin, P.* ; Gellerich, F.N.* ; Jacobs, H.T.* ; Braun, T.*

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

Dis. Model. Mech. 10, 163-171 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Plants and many lower organisms, but not mammals, express alternative oxidases (AOX) 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, whilst 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Mitochondria ; Mitochondrial Disease ; Respiratory Chain ; Alternative Oxidase; Alternative-oxidase; Native Electrophoresis; Protein Complexes; Acute Lethality; Human-cells; Mice; Mitochondria; Drosophila; Defects; Deficiency
Language english
Publication Year 2017
Prepublished in Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 1754-8403
e-ISSN 1754-8411
Journal Disease Models and Mechanisms
Quellenangaben Volume: 10, Issue: 2, Pages: 163-171 Article Number: , Supplement: ,
Publisher Company of Biologists
Publishing Place Cambridge
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute for Allergy Research (IAF)
Institute of Developmental Genetics (IDG)
Institute of Pathology (PATH)
POF-Topic(s) 30201 - Metabolic Health
30202 - Environmental Health
30204 - Cell Programming and Repair
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Genetics and Epidemiology
Allergy
Enabling and Novel Technologies
PSP Element(s) G-500600-001
G-500600-004
G-505400-001
G-500500-001
G-500500-002
G-500300-001
G-500692-001
PubMed ID 28067626
DOI 10.1242/dmm.027839
WOS ID WOS:000393913800008
Erfassungsdatum 2016-12-31
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