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

作者：Becker Lore; Kling Eva; Schiller Evelyn; Zeh Ramona; Schrewe Anja; Hoelter Sabine M; Mos**rugger Ilona; Calzada Wack Julia; Strecker Valentina; Wittig Ilka; Dumitru Iulia; Wenz Tina; Bender Andreas; Aichler Michaela; Janik Dirk; Neff Frauke; Walch Axel; Quintanilla Fend Leticia; Floss Thomas; Bekeredjian Raffi; Gailus Durner Valerie; Fuchs Helmut; Wurst Wolfgang; Meitinger Thomas; Prokisch Holger; de Angelis Martin Hrabe; Klopstock Thomas^*

来源：PLos One, 2014, 9(12): e114918.

DOI：10.1371/journal.pone.0114918

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.

• 出版日期2014-12-15