MTO1-Deficient Mouse Model Mirrors the Human Phenotype Showing Complex I Defect and Cardiomyopathy

Autor: Ilona Mossbrugger, Frauke Neff, Ilka Wittig, Evelyn Schiller, Wolfgang Wurst, Valentina Strecker, Andreas Bender, Anja Schrewe, Thomas Floss, Sabine M. Hölter, Valerie Gailus-Durner, Helmut Fuchs, Julia Calzada-Wack, Thomas Meitinger, Thomas Klopstock, Raffi Bekeredjian, Martin Hrabě de Angelis, Michaela Aichler, Tina Wenz, Holger Prokisch, Ramona Zeh, Lore Becker, Dirk Janik, Iulia Dumitru, Leticia Quintanilla-Fend, Eva Kling, Axel Walch
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
pathology [Myocardium]
Pathology
Heredity
Mitochondrial Diseases
Mitochondrial Myopathy
Mitochondrial translation
Physiology
Respiratory chain
Cardiomyopathy
Gene Dosage
Gene Expression
pathology [Cardiomyopathies]
Mitochondrion
genetics [Carrier Proteins]
Mto1 protein
mouse
Biochemistry
pathology [Mitochondria]
Oxidative Phosphorylation
Mice
Molecular Cell Biology
Medicine and Health Sciences
genetics [Electron Transport Complex I]
Energy-Producing Organelles
genetics [Cardiomyopathies]
Mice
Knockout
Multidisciplinary
Respiration
Hypertrophic cardiomyopathy
RNA-Binding Proteins
Heart
Animal Models
genetics [DNA
Mitochondrial]
Mitochondria
Phenotypes
Genes
Mitochondrial
Cardiovascular Diseases
Lactic acidosis
Gene Knockdown Techniques
Medicine
Female
Cardiomyopathies
Arrhythmia
Research Article
medicine.medical_specialty
Science
Cardiology
Mutagenesis (molecular biology technique)
Mouse Models
Bioenergetics
Research and Analysis Methods
Gene dosage
DNA
Mitochondrial
Mitochondrial Proteins
Oxygen Consumption
Model Organisms
medicine
Genetics
Animals
Humans
ddc:610
Clinical Genetics
physiopathology [Heart]
Electron Transport Complex I
business.industry
Myocardium
Biology and Life Sciences
Human Genetics
Cell Biology
physiopathology [Cardiomyopathies]
medicine.disease
metabolism [Mitochondria]
Mice
Inbred C57BL
Disease Models
Animal
Protein Translation
business
Physiological Processes
Carrier Proteins
Zdroj: PLOS ONE
PLoS ONE, Vol 9, Iss 12, p e114918 (2014)
PLOS ONE 9(12), e114918 (2014). doi:10.1371/journal.pone.0114918
PLoS ONE
PLoS ONE 9:e114918 (2014)
DOI: 10.1371/journal.pone.0114918
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: