Analysis Tools
behavior/neurological
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• 40 week old mice show decreased exploratory behavior
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• dragging of the feet is seen at 14 weeks of age, progresses with age and becomes increasingly more severe
• chronic treatment of males with 17-DMAG, an Hsp90 inhibitor, delays the onset and progression of foot-dragging
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• at 19 weeks of age, a large percentage of mice show hindlimb clasping
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• on the balance beam test, mice show a worse performance already at 10 weeks of age, showing a higher frequency of foot slips and flattened body posture on the beams with disease progression, and fail to maintain balance and fall off the beams by 40 weeks of age
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• mice show impairments on the rotarod starting at 20 weeks of age and by 40 weeks, show dramatic deterioration in performance on both the accelerating and constant speed rods
• chronic treatment with 17-DMAG delays the motor deficits in the rotarod, motor swimming, and balance beam test by about 8 weeks, however treatment does not affect weakness/hyponia, tremors and abnormal reflexes
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• mice swim slower than controls at 22-25 weeks of age and even more at 40 weeks of age
• mice exhibit abnormalities in swimming movements, adopting a twisted posture and kicking in an uncoordinated manner
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• mice show impairments in the hanging wire grip test that become worse with age, hanging for a shorter time at 7 and 19 weeks of age, and showing decreased grip strength at 19 weeks
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• seen at 40 weeks of age
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• mice start to show abnormal gait at 16 weeks of age
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• beginning at 16 weeks of age, mice show reduced paw overlap in footprint patterns, indicating an altered uniformity of step alternation and a decrease in stride length
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• 40 week old mice show decreased locomotor behavior
• however, mice exhibit normal performance in the Morris Water Maze
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growth/size/body
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• males show a lower body weight gain compared to control males at 19 weeks of age and show a decline in body weight after this age
• females show a lower body weight at 40 weeks of age but not at 19 weeks of age
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muscle
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• at 19 weeks of age, a large percentage of mice develop loss of hindlimb tonus resistance
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nervous system
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• reduction in brain volume at 60 weeks of age
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• total brain weight is reduced by 5% at 42-43 weeks of age, but not at 20 weeks
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• hyperchromatic cells and astrogliosis is seen in the substantia nigra at 60 weeks of age
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• atrophic and hyperchromatic neurons in the pontine nuclei are seen at 24 weeks of age and a decrease in total cell number in pontine nuclei is seen at 60 weeks of age
• chronic treatment with 17-DMAG reduces neuropathology in the CNS, with males showing normal cell morphology in the pontine nuclei
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astrocytosis
(
J:222991
)
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• astrogliosis is seen in the substantia nigra at 60 weeks of age
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• ataxin3 inclusions are seen in the nucleus of neuronal cells in different regions of the CNS at 20-35 weeks of age
• chronic treatment with 17-DMAG reduces neuropathology in the CNS, with males showing a reduction in cells that contain ataxin3 nuclear inclusions
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• in the pontine nuclei and substantia nigra by 60 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Machado-Joseph disease | DOID:1440 |
OMIM:109150 |
J:222991 | |
