Analysis Tools
behavior/neurological
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• at 18 months, some mutants displayed a dystonic posture of the hindlimbs when lifted by the tail
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• at one year of age, mutants on an alpha-tocopherol-normal and -deficient diet displayed a mild ataxia which worsened with increasing age
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• at 18 months, mutants displayed a significantly shorter step length, and poor performance on the accelerating rotating rod apparatus relative to wild-type
• performance on rotarod improved with alpha-tocopherol supplementation
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head shaking
(
J:90006
)
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• at one year of age, mutants on an alpha-tocopherol-normal and -deficient diet displayed head shaking; this phenotype became worse with increasing age
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embryo
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• at 10.5 dpc, live embryos in the uteri of pregnant homozygous null mice appeared abnormal, and the number of trophoblast cells was significantly reduced
• embryonic blood vessels were undetectable in the mutant trophoblast
• the placental failure was effectively reversed by alpha-tocopherol or synthetic antioxidant dietary supplement
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• at 10.5 dpc, the labyrinth region of placentas from pregnant homozygous null females was abnormally small
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homeostasis/metabolism
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• mutant brain tissues displayed increased lipid peroxidation relative to wild-type
• in particular, massive lipofuscin accumulation was observed in the dorsal root ganglion cells, the outer segment of photoreceptor cells, and the spinal anterior horn cells (i.e. in degenerating neurons)
• all these abnormalities were suppressed with alpha-tocopherol supplementation
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• when fed a normal diet (36 mg of alpha-tocopherol/kg diet), homozygous null mice displayed a 100% reduction in plasma vitamin E (alpha-tocopherol) concentration relative to wild-type
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muscle
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• at 18 months, some mutants displayed a dystonic posture of the hindlimbs when lifted by the tail
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• at 20 months, skeletal muscles displayed the presence of angulated atrophic fibers
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• at 20 months, skeletal muscles displayed variability in fiber size
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reproductive system
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• homozygous null females became pregnant after mating but failed to deliver offspring
• over 70% of embryos died in the uteri of homozygous null mice at 11.5 dpc
• the proportion of live embryos decreased significantly between 11.5 and 14.5 dpc
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vision/eye
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• at 20 months, the mutant retina contained disorganized photoreceptors displaying decreased thickness of the outer layer and the rod inner and outer segments
• these defects were exacerbated in mutant mice on an alpha-tocopherol-deficient diet, much more subtle in wild-type mice on a -deficient diet, and almost reversible upon alpha-tocopherol supplementation
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• retinal degeneration became evident at 20 months of age; no histological evidence of degeneration was noted at 12 months
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• ERGs revealed that both the a-wave (from Muller cells and inner neuronal layers) and b-waves (from photoreceptor cells) were significantly decreased in mutant mice maintained on a normal diet
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nervous system
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• in the spinal cord, anterior horn cells showed a mild degeneration with fibrillary gliosis
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• at 20 months, the mutant brain exhibited degeneration of the posterior column and posterior column nucleus with fiber loss, astrocytic proliferation, and abundance of axonal spheroids
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• on an alpha-tocopherol-deficient diet, the lumbar potential of somatosensory-evoked potentials (SEPs), originating from the spinal nerve roots, remained unaffected in mutant mice; in contrast, the cortical potential of SEPs almost disappeared in mutant mice relative to wild-type
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| familial isolated deficiency of vitamin E | DOID:0090028 |
OMIM:277460 |
J:67046 | |
