Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
ImmtGt(AW0256)Wtsi mutation
(0 available);
any
Immt mutation
(66 available)
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mortality/aging
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• no viable homozygotes are recovered from E10.5 on
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embryo
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• embryos exhibit massive apoptosis at E9.5
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• at E9.5, embryos show no clear shape
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• at E7.5, embryos are much smaller than wild-type controls
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growth/size/body
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• at E7.5, embryos are much smaller than wild-type controls
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cellular
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• embryos exhibit massive apoptosis at E9.5
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
ImmtGt(AW0256)Wtsi mutation
(0 available);
any
Immt mutation
(66 available)
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behavior/neurological
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• in the Morris water maze test, mice show impaired ability to locate the platform after training, as indicated by an increase in distance, latency and mean annulus crossing at 12 months of age
• however, grip strength and velocity are relatively normal
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• mice exhibit progressive neurological/motor dysfunction as early as 6 months of age
• however, mice are born in normal Mendelian ratios and show no apparent phenotype at birth
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• mice show an increase in the time to cross a balance beam and a higher number of hindfeet missteps at 3 and 6 months of age, indicating poor motor balance and coordination
• treatment with antioxidant N-acetylcysteine (NAC) for 1 year restores the time to cross and the number of hindfeet missteps to wild-type values
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• mice exhibit gait abnormalities with shorter stride length but increased hind base and matching at 6 and 12 months of age
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nervous system
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• cerebellar neurons exhibit abnormal mitochondrial morphology, with less condensed mitochondria matrix, vacuolation, and partial loss of mitochondrial cristae at 12 months of age
• treatment with antioxidant N-acetylcysteine (NAC) restores mitochondrial ultrastructure in cerebellar neurons
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• following exposure to X-ray irradiation at P7, cerebellar neurons show increased cell apoptosis relative to similarly treated wild-type cells
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• mice show partial enlargement of the lateral ventricles
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• mice show a significant reduction in hippocampus volume
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• mice with overt neurologic defects show a significant loss of cerebellar Purkinje cells at 12 months of age
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• mice show a trend towards decreased cerebellum volume
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• mice with overt neurologic defects show increased numbers of neurofibrillary tangles in the hippocampus, suggesting neurodegenerative changes
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• mice with overt neurologic defects show a marked reduction of dopaminergic neurons in the substantia nigra
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cellular
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• cerebellar neurons exhibit partial loss of mitochondrial cristae at 12 months of age
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• cerebellar neurons exhibit less condensed mitochondria matrix at 12 months of age
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• mice exhibit an increased density of mitochondria in muscle with relatively normal mitochondrial structure at 2 and 10 months of age
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• cerebellar neurons exhibit abnormal mitochondrial morphology, with less condensed mitochondria matrix, vacuolation, and partial loss of mitochondrial cristae at 12 months of age
• treatment with antioxidant N-acetylcysteine (NAC) restores mitochondrial ultrastructure in cerebellar neurons
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• following exposure to X-ray irradiation at P7, mice show markedly increased DNA damage response markers (phosphorylated 53BP1 and SMC1 foci formation) in the external granule cell layer (EGL) of proliferating cerebella and increased cell apoptosis in cerebellar neurons relative to similarly treated wild-type controls
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• following exposure to X-ray irradiation at P7, cerebellar neurons show increased cell apoptosis relative to similarly treated wild-type cells
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• mice show a significantly higher level of 18F-fluorodeoxyglucose (18F-FDG) uptake in brain, suggesting increased glucose transport in the neurons
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• cerebella neurons show a significant reduction in mitochondrial membrane potentials, suggesting impaired mitochondrial function
• NAC-treated mitochondria from cerebellar neurons exhibit an elevated O2 consumption and mitochondrial membrane potential at 10 months of age
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• cerebellar neurons exhibit alterations in mitochondrial oxidative phosphorylation complexes in an age-dependent manner
• respiratory control ratio (RCR) measured by mitochondrial state 3 (R3)/state 4 (R4) is significantly lower than in wild-type controls
• however, mtDNA copy number is normal at 2 and 10 months of age
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• aging mice exhibit significantly impaired OXPHOS function and ATP generation in brain
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• cerebellar neurons exhibit increased reactive oxygen species (ROS) from 3 to 24 months of age
• active endogenous oxidative stress is detected in cerebellar DNA and protein by 8-OHdG and nitrotyrosine staining, respectively, at 14 months of age
• treatment with antioxidant N-acetylcysteine (NAC) reduces ROS levels in P7 cerebellar mitochondria to levels seen in untreated wild-type controls
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homeostasis/metabolism
muscle
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• mice exhibit an increased density of mitochondria in muscle with relatively normal mitochondrial structure at 2 and 10 months of age
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