All Phenotypes Adck2<tm1(KOMP)Vlcg> MGI Mouse

abnormal adipose tissue amount ( J:280282 )

• visceral fat accumulation

• 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

decreased grip strength ( J:280282 )

• mice show a decline in two and four limb grip strength tests

• mice supplemented with CoQ10 show improved grip strength

impaired exercise endurance ( J:280282 )

• 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

abnormal mitochondrial physiology ( J:280282 )

• 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

increased mitochondrial fission ( J:280282 )

• succinate dehydrogenase and cytochrome c oxidase staining are increased in muscle fibers indicating mitochondrial proliferation

decreased fatty acid beta-oxidation ( J:280282 )

• 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

slow postnatal weight gain ( J:280282 )

• 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

impaired exercise endurance ( J:280282 )

• 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

abnormal homeostasis ( J:280282 )

• 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

decreased fatty acid beta-oxidation ( J:280282 )

• 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

decreased circulating carnitine level ( J:280282 )

• circulating concentrations of free carnitine are reduced

increased circulating lactate level ( J:280282 )

• increase in plasma lactate

• mice supplemented with CoQ10 show a decrease in plasma lactate levels

decreased circulating free fatty acids level ( J:280282 )

• decrease of free fatty acids such as linoleic, myristic, and palmitic in plasma

abnormal enzyme/coenzyme level ( J:280282 )

• 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

increased carbon dioxide production ( J:280282 )

increased oxygen consumption ( J:280282 )

increased respiratory quotient ( J:280282 )

increased fatty acids level ( J:280282 )

• circulating short- and long-chain fatty acid levels are increased

increased liver free fatty acids level ( J:280282 )

• accumulation of free fatty acids such as linoleic, myristic, and palmitic in tissues (especially stearic acid in the liver)

decreased glycerol level ( J:280282 )

organic aciduria ( J:280282 )

• urinary excretion of organic acids, including lactate, malate, fumarate, alpha-ketoglutarate, succinate, adipic acid, ethylmalonic acid, and hexanoylglycine, is increased

increased liver free fatty acids level ( J:280282 )

• accumulation of free fatty acids such as linoleic, myristic, and palmitic in tissues (especially stearic acid in the liver)

macrovesicular hepatic steatosis ( J:280282 )

• liver shows accumulation of large lipid droplets in periportal and perivenular hepatocytes

increased variability of skeletal muscle fiber size ( J:280282 )

• gastrocnemius muscle shows a mild variation in fiber size and some fibers appear as ragged red fibers

abnormal muscle physiology ( J:280282 )

• 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

organic aciduria ( J:280282 )

• urinary excretion of organic acids, including lactate, malate, fumarate, alpha-ketoglutarate, succinate, adipic acid, ethylmalonic acid, and hexanoylglycine, is increased

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mitochondrial myopathy		DOID:699	OMIM:251900	J:280282

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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