Analysis Tools
homeostasis/metabolism
| N |
• mice exhibit normal exercise capacity and endurance in a treadmill test both at 4-6 weeks and at 30 weeks of age
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• in organello translation assays show decreased levels of the 13 mtDNA-encoded polypeptides in liver mitochondria from 6- to 8-week-old mice, indicating a reduced mitochondrial protein synthesis rate
• levels of two mitoribosome proteins (MRPL13 and MRPS9) are significantly increased in liver, likely as a response to the mitochondrial translation defect
• however, no reductions in mitochondrial translation are detected in brain or kidney mitochondria, consistent with the normal respiratory chain enzyme activities observed in these organs
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• some male mice show a moderate increase in plasma alanine aminotransferase (ALT) levels from 24 to 40 weeks of age, with no increase in plasma ALT detected in female mice
• however, H&E staining of liver sections shows signs of nonalcoholic steatohepatitis comparable to those in wild-type males at 50 weeks of age
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• mitochondria-enriched extracts from brain, liver, heart, and kidney show a ~85% reduction in GFM1/EFG1 protein levels; similar reductions are noted in protein extracts from total homogenates of liver, brain, and skeletal muscle tissue, with no change of steady-state mRNA levels detected in any tissue
• however, total mRNA and mitochondrial protein levels of other mitochondrial translation elongation and termination factors are not altered in any tissue
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• 6- to 8-week-old mice show a ~40% reduction in respiratory chain complex IV enzyme activity (normalized to citrate synthase activity) in the liver
• however, enzyme activity of other OXPHOS complexes (complex I, complex II, complex III, and complex II plus III) and citrate synthase activity are normal in liver
• moreover, no changes in respiratory chain enzyme activities are detected in brain, kidney, skeletal muscle or heart
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• 6- to 8-week-old mice show a ~40% reduction in respiratory chain complex IV enzyme activity (normalized to citrate synthase activity) in the liver
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cellular
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• analysis of OXPHOS subunits levels by BN-PAGE and immunodetection using complex-specific antibodies shows a significant reduction in the relative amount of complex IV in liver mitochondria, with no change in the relative amount of other complexes
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• in organello translation assays show decreased levels of the 13 mtDNA-encoded polypeptides in liver mitochondria from 6- to 8-week-old mice, indicating a reduced mitochondrial protein synthesis rate
• levels of two mitoribosome proteins (MRPL13 and MRPS9) are significantly increased in liver, likely as a response to the mitochondrial translation defect
• however, no reductions in mitochondrial translation are detected in brain or kidney mitochondria, consistent with the normal respiratory chain enzyme activities observed in these organs
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liver/biliary system
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• 6- to 8-week-old mice show a ~40% reduction in respiratory chain complex IV enzyme activity (normalized to citrate synthase activity) in the liver
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reproductive system
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• mice stop to reproduce
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mortality/aging
| N |
• mice are born in expected Mendelian ratios and show no significant differences in long-term survival relative to wild-type and heterozygous controls
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growth/size/body
| N |
• both sexes show normal body weight up to 50 weeks of age; relative organ weights expressed as % of total body weight are normal at 6-8 weeks of age
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behavior/neurological
| N |
• mice exhibit normal motor coordination performance in a hanging wire test both at 4-6 weeks and at 30 weeks of age
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muscle
| N |
• mice exhibit normal muscle strength in a weight-lift test both at 4-6 weeks and at 30 weeks of age
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