Analysis Tools
adipose tissue
 |
• visceral fat accumulation
|
behavior/neurological
|
|
• 12 month old mice show poorer coordination on a rotarod
• however, mice show unaltered nociceptive response in the hot-plate test, normal fear-conditioning, and only a tendency toward more extensive exploratory behavior
|
|
|
• mice show a decline in two and four limb grip strength tests
• mice supplemented with CoQ10 show improved grip strength
|
|
|
• 12 month old mice show reduced overall endurance, as seen by shorter running distance on a treadmill due to exhaustion
• mice supplemented with CoQ10 show improvement in treadmill endurance exercise time
|
cellular
|
|
• MEFs show a decrease in mitochondrial complexes III, II+III, and IV activities
• mitochondrial complex I+III and II+III activities are decreased in skeletal muscle, but the activities of the individual complexes are normal
• mitochondrial complex I, II, and I+III activities are higher in kidney mitochondria, while those of complex III, IV, and II+III are not affected
• oxygen consumption rate shows a difference in basal and maximum respiration in MEFs when glucose is used as a substrate
• however, mitochondrial respiratory complexes are unaffected in the brain and liver
|
|
|
• succinate dehydrogenase and cytochrome c oxidase staining are increased in muscle fibers indicating mitochondrial proliferation
|
|
|
• mice show a decrease in mitochondrial fatty acid beta-oxidation
• MEFs do not show increased proliferation when fatty acids are added to medium at low glucose concentrations as is seen in wild-type MEFs and addition of fatty acids to glucose-free medium causes more than 50% growth arrest compared to wild-type cells
• palmitate-dependent oxygen consumption rate is decreased in permeabilized MEFs compared to wild-type cells
• circulating concentrations of beta-hydroxybutyrate and free carnitine are reduced
|
growth/size/body
|
|
• pups weight less at weaning than wild-type pups
• however, mice show a trend toward greater weight gain with age and no difference in body weight was seen at later time points
|
homeostasis/metabolism
|
|
• 12 month old mice show reduced overall endurance, as seen by shorter running distance on a treadmill due to exhaustion
• mice supplemented with CoQ10 show improvement in treadmill endurance exercise time
|
|
|
• mice show higher oxygen consumption, carbon dioxide production, and respiratory exchange ratio, indicating a greater use of carbohydrates in mutants compared to a consumption of a mix of fat and carbohydrates by wild-type mice
|
|
|
• mice show a decrease in mitochondrial fatty acid beta-oxidation
• MEFs do not show increased proliferation when fatty acids are added to medium at low glucose concentrations as is seen in wild-type MEFs and addition of fatty acids to glucose-free medium causes more than 50% growth arrest compared to wild-type cells
• palmitate-dependent oxygen consumption rate is decreased in permeabilized MEFs compared to wild-type cells
• circulating concentrations of beta-hydroxybutyrate and free carnitine are reduced
|
|
|
• circulating concentrations of free carnitine are reduced
|
|
|
• increase in plasma lactate
• mice supplemented with CoQ10 show a decrease in plasma lactate levels
|
|
|
• decrease of free fatty acids such as linoleic, myristic, and palmitic in plasma
|
|
|
• MEFs show a reduction in CoQ9 and CoQ10 levels and in their biosynthetic rates
• CoQ9 and CoQ10 levels are decreased in skeletal muscle and a downward trend is seen in the heart and liver, but not in the brain or kidney
|
|
|
• circulating short- and long-chain fatty acid levels are increased
|
|
|
• accumulation of free fatty acids such as linoleic, myristic, and palmitic in tissues (especially stearic acid in the liver)
|
|
|
• urinary excretion of organic acids, including lactate, malate, fumarate, alpha-ketoglutarate, succinate, adipic acid, ethylmalonic acid, and hexanoylglycine, is increased
|
liver/biliary system
|
|
• accumulation of free fatty acids such as linoleic, myristic, and palmitic in tissues (especially stearic acid in the liver)
|
|
|
• liver shows accumulation of large lipid droplets in periportal and perivenular hepatocytes
|
muscle
|
|
• gastrocnemius muscle shows a mild variation in fiber size and some fibers appear as ragged red fibers
|
|
|
• accumulation of pyruvate and lactate in plasma and skeletal muscle
• succinate dehydrogenase and cytochrome c oxidase staining are increased in muscle fibers indicating mitochondrial proliferation
|
renal/urinary system
|
|
• urinary excretion of organic acids, including lactate, malate, fumarate, alpha-ketoglutarate, succinate, adipic acid, ethylmalonic acid, and hexanoylglycine, is increased
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| mitochondrial myopathy | DOID:699 |
OMIM:251900 |
J:280282 | |
