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Phenotypes Associated with This Genotype
involves: 129S7/SvEvBrd * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ttpatm1Hsz mutation (0 available); any Ttpa mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Histological findings indicating neurodegeneration in Ttpatm1Hsz/Ttpatm1Hsz mice

• at 18 months, mutant showed tremors
• at one year of age, mutants on an alpha-tocopherol-normal and -deficient diet displayed a mild ataxia which worsened with increasing age
• 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
• at 18 months, some mutants displayed a dystonic posture of the hindlimbs when lifted by the tail
• at one year of age, mutants on an alpha-tocopherol-normal and -deficient diet displayed head shaking; this phenotype became worse with increasing age
• at 18 months, mutants exhibited paresis in the hindlimbs while walking

• 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
• at 10.5 dpc, the labyrinth region of placentas from pregnant homozygous null females was abnormally small

• 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
• 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

• at 18 months, some mutants displayed a dystonic posture of the hindlimbs when lifted by the tail
• at 20 months, skeletal muscles displayed the presence of angulated atrophic fibers
• at 20 months, skeletal muscles displayed variability in fiber size

reproductive system
• 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

• 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
• retinal degeneration became evident at 20 months of age; no histological evidence of degeneration was noted at 12 months
• 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

nervous system
• in the spinal cord, anterior horn cells showed a mild degeneration with fibrillary gliosis
• 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
• 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

Mouse Models of Human Disease
OMIM ID Ref(s)
Vitamin E, Familial Isolated Deficiency Of; VED 277460 J:67046

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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
MGI 6.03
The Jackson Laboratory