Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pitx3tm1.1Cai mutation
(1 available);
any
Pitx3 mutation
(22 available)
Tg(tetO-SNCA*A53T)E2Cai mutation
(1 available)
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nervous system
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• at 1 month, midbrain dopamine (mDA) neurons exhibit enlarged axon terminals compared with control cells
• at 12 months, mDA neurons exhibit perturbations of the Golgi apparatus compared with control mice
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• progressive degeneration of midbrain dopamine neurons as early as 1 month
• however, there is no loss of midbrain dopamine neurons between 12 and 20 months and inhibition of Nurr1 (Nr4a2) ameliorates loss of neurons
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• at 12 months, neurites exhibit reduced length and complexity compared with control neurites
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• progressive degeneration of midbrain dopamine neurons as early as 1 month
• however, there is no loss of midbrain dopamine neurons between 12 and 20 months
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• in the soma and neurites of midbrain dopamine neurons at 12 and 18 months
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• midbrain dopamine neurons exhibit impaired
• autophagy/lysosomal pathways and ubiquitin proteasome system pathway compared with control cells
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• severely impaired in the striatum
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behavior/neurological
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• on a rotarod at 2 months
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• unsteady and shorter at 1 month
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• at 1 months
• however, mice fed doxycycline treatment rescues rearing impairment
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• moderate starting at 2 months in an open field
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cellular
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• impaired autophagy/lysosome pathways in midbrain dopamine neurons
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growth/size/body
hematopoietic system
homeostasis/metabolism
immune system
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pink1tm1Zhzh mutation
(0 available);
any
Pink1 mutation
(42 available)
Slc6a3tm4.1(tTA)Xz mutation
(1 available);
any
Slc6a3 mutation
(66 available)
Tg(tetO-SNCA*A53T)E2Cai mutation
(1 available)
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cellular
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• 51% reduction of mitochondrial mass at 3 weeks of age
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nervous system
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• "mitochondrial inclusions are observed in in dopaminergic neurons beginning at 3 weeks of age
• inclusions average 4.2 um in diameter and are labeled by mitochondrial markers (COX1, SOD2)
• number of inclusions is approximately 1.4 inclusions per dopaminergic neuron
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a3tm4.1(tTA)Xz mutation
(1 available);
any
Slc6a3 mutation
(66 available)
Tg(tetO-SNCA*A53T)E2Cai mutation
(1 available)
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nervous system
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• 21% dopaminergic neuron loss in the substantia nigra pars compacta (SNc) by 3 months of age
• 35% loss by 6 months of age
• loss appears to stop or slow between 6 and 12 months
• dopamine turnover rate is increased by 29%
• decrease in TH (tyrosine hydroxylase) terminal staining in the dorsal, but not ventral, striatum of 12 month old mice
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• 25 fold increase in enlarged axon varicosities in midbrain region at 6 weeks of age
• varicosities are approximately 10 um in diameter, are oval-shaped and have a hollowed core
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• fragmented dendrites are observed in the substantia nigra pars reticulata at 6 weeks of age
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• "mitochondrial inclusions" are observed in dopaminergic neurons beginning at 3 weeks of age
• inclusions are 0.5-2 um in diameter and are labeled by mitochondrial markers (COX1, SOD2)
• number of inclusions is approximately 1.6 inclusions per dopaminergic neuron at 3 weeks of age
• inclusions are distributed in soma and proximal processes of dopaminergic neurons
• inclusions are mostly restricted to substantia nigra pars compacta
• the number of inclusions is decreased by 6 months of age
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growth/size/body
homeostasis/metabolism
cellular
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• mitochondria in dopaminergic neurons appears fragmented by 6 weeks of age
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• mitochondrial length is decreased by 61% in mitochondria from dopaminergic neurons, however, mitochondrial mass is similar to controls
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• multiple senescent mitochondria are observed in dopaminergic neurons as compared to controls
• senescent mitochondria exhibit disordered cristae, swollen matrix and the absent outer membranes
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nervous system
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• "mitochondrial inclusions are observed in in dopaminergic neurons beginning at 3 weeks of age
• inclusions average 4.4 um in diameter and are labeled by mitochondrial markers (COX1, SOD2)
• number of inclusions is approximately 1.7 inclusions per dopaminergic neuron
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cellular
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• 57% reduction of mitochondrial mass at 3 weeks of age
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nervous system
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• somatic alpha synuclein in neurons is apparent at 12 months
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• increased microglial activation is observed in the brain at 12 months
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• numbers of residual neurons is significantly lower than non transgenic controls
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• significant at 12 months
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• the Golgi complex shows severe fragmentation in 12 month old animals
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• neurodegeneration significant at 12 months
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immune system
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• increased microglial activation is observed in the brain at 12 months
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hematopoietic system
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• increased microglial activation is observed in the brain at 12 months
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nervous system
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• no apparent neurodegeneration is observed in 12-month old mice; no significant elevation of astrocytosis, microgliosis or somatic accumulation of alpha-synuclein is detected in striatum at 12 months
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation
(8 available)
Tg(tetO-LRRK2)C77Cai mutation
(0 available)
Tg(tetO-SNCA*A53T)E2Cai mutation
(1 available)
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nervous system
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• increasing accumulation of alpha-synuclein is detected in cell bodies in brains of A53T/LRRK2WT-L at 1 month compared to LRRK2WT-L animals
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• increased microglial activation is observed in the brain
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• A53T/LRRK2WT-L mice show significant elevation of GFAP-positive astrocytes in the striatum compared to A53T mice
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• neurodegeneration is accelerated in the striatum
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• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month
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behavior/neurological
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• mice show no apparent motor phenotype up to 6 months of age
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hematopoietic system
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• increased microglial activation is observed in the brain
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immune system
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• increased microglial activation is observed in the brain
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation
(8 available)
Tg(tetO-LRRK2*)D10Cai mutation
(0 available)
Tg(tetO-SNCA*A53T)E2Cai mutation
(1 available)
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nervous system
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• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month in A53T/KD mice compared to KD animals
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• increased framentation of the Golgi complex is observed
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• neuropathology is accelerated in A53T/KD mice compared to A53T mice
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation
(8 available)
Tg(tetO-LRRK2*G2019S)E3Cai mutation
(1 available)
Tg(tetO-SNCA*A53T)E2Cai mutation
(1 available)
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nervous system
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• substantial accumulation of alpha-synuclein is detected in cell bodies at 1 month
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• exacerbated in the striatum compared to A53T mice at 1 month of age
• levels of microglial activation are higher than in A53T/LRRK2WT mice
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• exacerbated in the striatum compared to A53T mice at 1 month of age
• levels of GFAP-positive cells are higher than in A53T/LRRK2WT mice
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• the Golgi complex is drastically altered in neurons at 1 month with severely fragmented
• at 1 month, the medial/trans-Golgi in neurons is severely fragmented
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• in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to controls or A53T mice (seen with 3.5x greater frequency than in A53T mice); these mitochondria are not functional
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• a significant increase in detergent-insoluble high molecular weight (HMW) alpha synuclein is detected in 1 month old mice compared to A53T age-matched mice
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• exacerbated in the striatum compared to A53T mice at 1 month of age
• dramatic loss (>85%) of striatal neurons is seen in the dorsal striatum
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hematopoietic system
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• exacerbated in the striatum compared to A53T mice at 1 month of age
• levels of microglial activation are higher than in A53T/LRRK2WT mice
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immune system
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• exacerbated in the striatum compared to A53T mice at 1 month of age
• levels of microglial activation are higher than in A53T/LRRK2WT mice
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cellular
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• in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to controls or A53T mice (seen with 3.5x greater frequency than in A53T mice); these mitochondria are not functional
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation
(8 available)
Tg(tetO-LRRK2)C7874Cai mutation
(2 available)
Tg(tetO-SNCA*A53T)E2Cai mutation
(1 available)
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nervous system
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• increasing accumulation of alpha-synuclein is detected in cell bodies at 1 month compared to A53T/LRRK2WT-L animals
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• increased microglial activation is observed in the brain
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• neuron loss is detected at 6 months and later
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• A53T/LRRK2WT mice show significant elevation of GFAP-positive astrocytes in the striatum compared to A53T mice
• more GFAP-positive astrocytes are found in the brain than in A53T/LRRK2WT-L brains
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• the Golgi complex is drastically altered in neurons at 1 month with severely fragmented cis-Golgi
• at 1 month, the medial/trans-Golgi in neurons is severely fragmented
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• neurodegeneration is accelerated in the striatum
• dramatic loss (>80%) of striatal neurons is seen in the dorsal striatum
• most degenerating neurons are striatal medium-sized spiny neurons (MSN)
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• neuropathology is accelerated in mice compared to A53T mice
• in 6 month old mice, elevated levels of ubiquitin are detected in somas and nuclei of cortical neurons; levels of alpha-synuclein and ubiquitin are slightly higher than in A53T mutant mice
• brain homogenates contain significantly elevated levels of ubiquitinated proteins at 3 months
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immune system
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• increased microglial activation is observed in the brain
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hematopoietic system
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• increased microglial activation is observed in the brain
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Camk2a-tTA)1Mmay mutation
(8 available)
Tg(tetO-SNCA*A53T)E2Cai mutation
(1 available)
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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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• 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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• 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
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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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immune system
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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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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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