Analysis Tools
growth/size/body
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• A53T mice weigh significantly less than non transgenic mice and Tg(tetO-SNCA*A53T)E2Cai or Tg(Camk2a-tTA)1Mmay single mutants starting at 4 months of age
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behavior/neurological
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• mice display elevated rearing activities at 6 months of age
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• at 2 months of age, mice show drastically increased ambulatory activity
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nervous system
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• only a few neurons in the brain display alpha-synuclein staining in the cell body at 3 months; somatic accumulation becomes more prominent at 20 months; whereas no accumulation is detected in cell bodies at 1 month
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression
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microgliosis
(
J:156512
)
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• significant at 12 months
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression
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• neuron loss is detected at 6 months and later
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression
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• neuron loss is detected at 6 months and later
• in 6 month old mice but not in nontransgenic controls, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons, but
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astrocytosis
(
J:156512
)
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• significant at 12 months
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression
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• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented
• significant increase in Golgi fragmentation is observed at 6 months
• at 1 month, the medial/trans-Golgi in neurons is significantly altered with ratio of fragmented trans-Golgi significantly increased compared to non-transgenic animals
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression
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• in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to non-transgenic controls; these mitochondria are not functional
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• a significant increase in detergent-insoluble high molecular weight (HMW) alpha synuclein is detected in 12 month old mice compared to 1 month old mice
• significant decrease in HMW alpha-synuclein in total brain homogenates is observed when animals are treated with doxycycline to inhibit transgene expression
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• widespread degeneration is observed at 20 months
• age-dependent, progressive neurodegeneration occurs
• neuronal loss is detected in the frontal cortex (>80%) and dorsal striatum (>74%) at 20 months
• a significant reduction (>30%) of striatal neurons is seen at 6 months
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• while 3-month old A53T mice show no abnormal neuropathology, but neuropathology is evident at 12 and 20 months
• in 6 month old mice, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons; at 20 monts, a punctate staining pattern at neuronal processes is observed
• brain homogenates contain significantly elevated levels of ubiquitinated proteins at 3 months
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hematopoietic system
microgliosis
(
J:156512
)
|
• significant at 12 months
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression
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immune system
microgliosis
(
J:156512
)
|
• significant at 12 months
• significant rescue of phenotype is observed when animals are treated with doxycycline to inhibit transgene expression
|
cellular
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• in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to non-transgenic controls; these mitochondria are not functional
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