| 27377 | O88967 | YMEL1_MOUSE | ATP-dependent zinc metalloprotease YME1L1 (EC 3.4.24.-) (ATP-dependent metalloprotease FtsH1) (YME1-like protein 1) | DISRUPTION PHENOTYPE | Complete embryonic lethality; embryos present a clear developmental delay at 8.5 dpc, and the hearts of mutant embryos fail to beat properly at 9.5 and 10.5 dpc. Cardiomyocyte-specific gene disruption gives rise to animals that develop dilated cardiomyopathy and myocardial fibrosis at about 20 weeks after birth; mutants have a median life span of about 46 weeks, much shorter than wild-type. Mitochondria from mutant cardiomyocytes are smaller than normal, but have normal cristae architecture and display no significant difference in the assembly of respiratory complexes. Keeping mice with a cardiomyocyte-specific gene disruption on a high-fat diet leads to weight gain and reduced glucose tolerance, and prevents the development of cardiomyopathy. Mice with Yme1l gene disruption in cardiomyocytes and skeletal muscle have a median life span of 125 weeks, similar to wild-type. Their heart function is normal, in spite of the presence of fragmented mitochondria due to the loss of Opa1 cleavage at position S2. Skeletal muscle mitochondrial dysfunction is known to be associated with impaired insulin signaling and glucose intolerance, and as expected, these mice display impaired glucose homeostasis with decreased fasting insulin levels in the blood serum and glucose intolerance. Mice with a double, cardiomyocyte-specific gene disruption of Yme1l and Oma1 have normal cardiac function and do not display myocardial fibrosis. Likewise, cardiomyocyte mitochondria have normal morphology. Mice with a skeletal muscle Yme1l gene disruption plus a double, cardiomyocyte-specific gene disruption of Yme1l and Oma1 display normal glucose tolerance. {ECO:0000269|PubMed:26785494}. |