Analysis Tools
behavior/neurological
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• both young and adult males and females show lower forelimb grip strength
• oral dNTP supplementation improves forelimb grip strength
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cardiovascular system
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• mice exhibit enlarged hearts with lower left ventricular wall thickness
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cellular
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• lower mtDNA content in the liver, skeletal muscle, and brain
• oral dNTP supplementation increases mtDNA content in the liver
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• in the liver
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• in the liver
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• primary hepatocytes exhibit impaired mitochondrial respiration
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• mitochondrial fission machinery is not induced in the liver
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• mice show impaired mitochondrial oxidative phosphorylation: liver shows a reduction in mitochondrial CIII and V activity and impaired mitochondrial respiratory chain supercomplex assembly at 1 month of age
• brain and skeletal muscle show impaired mitochondrial supercomplex assembly at 6 months, but not 3 months, of age
• oral dNTP supplementation restores activity of subunits CI and CIV and partially rescues activity of CIII in the liver
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hearing/vestibular/ear
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• males show increased auditory brainstem response threshold to click noises at 3 and 6 months of age
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• adult and middle-aged male mice exhibit a hearing impairment
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homeostasis/metabolism
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• 1- to 6-month-old mice show an increased accumulation of hepatic glycogen
• the increase in hepatic glycogen is abolished by oral dNTP supplementation
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• mice show increased accumulation of hepatic cholesterol over time
• the increase in hepatic cholesterol is abolished by oral dNTP supplementation
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• accumulation of triacylglycerol in the liver
• the accumulation of triacylglycerol in the liver is partially reduced by oral dNTP supplementation
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• young and adult males have higher urinary 3-methylglutaconic acid (3-MGA) content indicating urinary 3-methylgutaconic aciduria
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liver/biliary system
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• mice show a late-onset lipid accumulation by 12 months of age
• liver shows fragmented and shrunken mitochondria
• number of mitochondria is higher in the liver
• however, hepatic lipid accumulation is not seen at 1 or 6 months
• however, hepatic fibrosis is not seen in 1- to 12-month-old mice
• decrease of phosphatidylglycerol (34:1) content in the liver at 2.5 months
• oral dNTP supplementation improves mitochondrial cristae structure and slightly improves mitochondrial morphology
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• 1- to 6-month-old mice show an increased accumulation of hepatic glycogen
• the increase in hepatic glycogen is abolished by oral dNTP supplementation
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• mice show increased accumulation of hepatic cholesterol over time
• the increase in hepatic cholesterol is abolished by oral dNTP supplementation
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• the accumulation of triacylglycerol in the liver is partially reduced by oral dNTP supplementation
• accumulation of triacylglycerol in the liver
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• hepatic cell edema occurs as early as 1 month of age and an advanced phenotype with damaged hepatic cells is seen at 12 months of age
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muscle
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• mice exhibit enlarged hearts with lower left ventricular wall thickness
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• decrease in the whole muscle cross-sectional area, including both fast and slow muscle fibers, and an increase in the slow to fast muscle fiber ratio
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• mice held a suspension rope with either the tail or hindlimb more poorly than wild-type mice in a modified forelimb suspension test, indicating decreased muscle strength
• mice supplemented with deoxy-ribonucleoside triphosphate (dNTP) via drinking water showed improved performance on the pole test, in the beam walking paw slip test, and the rotarod test
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nervous system
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• 12-month-old mice exhibit lesions in the basal ganglia
• percentage of IBA1-labeled microglia in basal ganglia of 6-month-old mice is lower
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brain lesion
(
J:326672
)
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• brain lesions are reminiscent of metabolic encephalopathy and mice develop a Leigh-like syndrome
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• brain lesions are associated with higher lactic acid content in the brain and a reminiscent of metabolic encephalopathy
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renal/urinary system
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• young and adult males have higher urinary 3-methylglutaconic acid (3-MGA) content indicating urinary 3-methylgutaconic aciduria
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reproductive system
| N |
• male fecundity does not appear to be affected
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growth/size/body
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome | DOID:0110001 |
OMIM:614739 |
J:326672 | |
