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Abstract:
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.
