MTO1-deficient mouse model mirrors the human phenotype showing complex I defect and cardiomyopathy

Recently, mutations in the mitochondrial translation optimization factor 1 gene (MTO1) were identified as causative in children with hypertrophic cardiomyopathy, lactic acidosis and respiratory chain defect. Here, we des
Recently, mutations in the mitochondrial translation optimization factor 1 gene (MTO1) were identified as causative in children with hypertrophic cardiomyopathy, lactic acidosis and respiratory chain defect. Here, we describe an MTO1-deficient mouse model generated by gene trap mutagenesis that mirrors the human phenotype remarkably well. As in patients, the most prominent signs and symptoms were cardiovascular and included bradycardia and cardiomyopathy. In addition, the mutant mice showed a marked worsening of arrhythmias during induction and reversal of anaesthesia. The detailed morphological and biochemical workup of murine hearts indicated that the myocardial damage was due to complex I deficiency and mitochondrial dysfunction. In contrast, neurological examination was largely normal in Mto1-deficient mice. A translational consequence of this mouse model may be to caution against anaesthesia-related cardiac arrhythmias which may be fatal in patients.
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Author:Lore Becker, Eva Kling, Evelyn Schiller, Ramona Zeh, Anja Schrewe, Sabine M. Hölter, Ilona Mossbrugger, Julia Calzada-Wack, Valentina Strecker, Ilka Wittig, Iulia Dumitru, Tina Wenz, Andreas Bender, Michaela Aichler, Dirk Janik, Frauke Neff, Axel Walch, Leticia Quintanilla-Fend, Thomas Floss, Raffi Bekeredjian, Valérie Gailus-Durner, Helmut Fuchs, Wolfgang Wurst, Thomas Meitinger, Holger Prokisch, Martin Hrabé de Angelis, Thomas Klopstock
URN:urn:nbn:de:hebis:30:3-364294
DOI:http://dx.doi.org/10.1371/journal.pone.0114918
ISSN:1932-6203
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25506927
Parent Title (English):PLoS One
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2014/12/15
Date of first Publication:2014/12/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2015/01/16
Volume:9
Issue:(12):e114918
Pagenumber:25
Note:
Copyright: © 2014 Becker et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS PPN:367474190
Institutes:Center for Membrane Proteomics (CMP)
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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