| Type | disruption phenotype | Description | Mice show a reduction in lifespan and develop heart hypertrophy (PubMed:18239138). The mean and maximum lifespan is reduced by 59% and 55% (PubMed:18239138). Mice develop kyphosis and lose subcutaneous fat early in life; they also show a general decrease in stress-resistance mechanisms (PubMed:18239138). Mice suffer from degenerative heart hypertrophy and inflammatory cardiomyopathy (PubMed:18239138). Hearts are also characterized by an extensive fibrosis (PubMed:18239138). Mice also display multisystemic mitochondrial dysfunction, characterized by increased blood lactate levels, reduced exercise performance, cardiac dysfunction, hepatic microvesicular steatosis and age-related hearing loss (PubMed:25200183). Cells show impaired oxidative phosphorylation (OxPhos) (PubMed:25200183). A substantial proportion of mice also show perinatal lethality and an accelerated aging phenotype, probably caused by increased replication stress and impaired DNA caused repair (PubMed:27225932). Females display reduced fertility and produce fewer oocytes and ovulate fewer eggs (PubMed:31256246). Oocytes show impaired meiotic progression with reduced levels of crossovers and chromosome synapsis defects (PubMed:31256246). Mice also show severe osteopenia characterized by decreased bone formation and an increase of osteoclasts (PubMed:30026585). |
