Journal
PLOS ONE
Volume 9, Issue 12, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0114918
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Funding
- German Federal Ministry of Education and Research (BMBF, Bonn, Germany) grants (mitoNET) [01GM1113A-C]
- National Genome Research Net (NGFN-Plus) [01GS0850, 01GS0851, 01GS0854]
- German Center for Vertigo and Balance Disorders [01EO0901]
- EU grants (EUMODIC) [LSHG-2006-037188, 211404, 01KX1012]
- Emmy-Noether-Programm of the Deutsche Forschungsgemeinschaft
- Deutsche Forschungsgemeinschaft [Sonderforschungsbereich 815]
- Cluster of Excellence Frankfurt Macromolecular Complexes at the Goethe University Frankfurt DFG project [EXC 115]
- Helmholtz Alliance for Mental Health in an Ageing Society (HelMA) through the Initiative and Network Fund of the Helmholtz Association
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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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