Analysis Tools|
Allele Symbol Allele Name Allele ID |
Tg(Pcp2-cre)2Mpin transgene insertion 2, Max-Planck-Institute of Neurobiology MGI:2137515 |
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| Summary |
51 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Neurodegeneration in Vps18tm1.1Wtao/Vps18tm1.1Wtao Tg(Nes-cre)1Kln/0 and Vps18tm1.1Wtao/Vps18tm1.1Wtao Tg(Pcp2-cre)2Mpin/0 brains
| N |
• Purkinje cells proliferation is normal
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• dramatic loss at 1 month
• very few Purkinje cells are present at 3 months
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• beginning at 3 weeks of age with the majority of cells absent at 4 weeks of age and no Purkinje cells by 7 months
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• absent by 7 months
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not exhibit premature death
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| N |
• Purkinje cells exhibit normal electrophysiology
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• as early as 5.5 to 7 weeks, mice exhibit loss of Purkinje cells unlike wild-type mice
• by 10 weeks, mice exhibit a 15% loss of Purkinje cells in lobule X compared with wild-type mice
• however, no further loss of Purkinje cells in lobule X occur between 10 and 20 weeks
• Purkinje cell loss in lobules II-V is greater than 75% at 10 weeks and approaches 100% by 15 weeks
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• by 10 weeks, mice exhibit difficulties traversing a balance beam unlike wild-type mice
• by 15 weeks, mice exhibit impaired performance on a rotarod compared with wild-type mice
• motor defects are age-dependent
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• mice exhibit age-dependent unesterified cholesterol accumulation in Purkinje cells unlike in wild-type mice
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| N |
• mice do not exhibit weight loss
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at 2-5 months of age, mice exhibit normal spatial learning in the hidden version of the Morris water maze with a clear preference for the platform quadrant during the probe trial and a similar reduction in latency times during training relative to control littermates
• in addition, mice display intact contextual fear conditioning relative to control littermates
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mutants exhibit normal hind limb extension in tail suspensions assays
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• mutants develop a mildly uncoordinated gait with wider paired distance
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• the cerebellar vermis is smaller
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Purkinje cell death in 9 weeks-old mutant mice cerebella
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• Purkinje cell dendrite attenuation in 9 weeks-old mutant mice cerebella
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• decreased cytochrome C oxidase activity and increased succinate dehydrogenase activity in Purkinje cells of 9-weeks-old mutant mice indicating the electron transport chain dysfunction in mitochondria
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• a progressive decline in coordination and balance in rotarod test
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• at 2 months of age, they begin to exhibit a slightly shaky gait
• mutants are indistinguishable from wild-type littermates first 2 mo
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• obvious neuro-degeneration of cerebella over time
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• ultrastructurally the mitochondria in mutant Purkinje cells shows dramatic defects in mitochondrial morphology, distribution, and cristae organization
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• the dendrites and death of Purkinje cell bodies resulting in very few surviving Purkinje cells by 3 months
• essentially all Purkinje cells are gone at 6 months of age
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• by 7 weeks, Purkinje cell axons show extensive torpedoes, focal swellings typical of many neuropathies
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• Purkinje cell dendrite attenuation in 9 weeks-old mutant mice cerebella
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• by 3 months of age, the mutant cerebella are only 75% that of wild-type
• by 1 year of age, the overall cerebellar area of mutants has dropped to 50% of wild-type
• the greatest loss occurs in the molecular layer
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• ultrastructurally the mitochondria in mutant Purkinje cells shows dramatic defects in mitochondrial morphology, distribution, and cristae organization
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• ecreased cytochrome C oxidase activity and increased succinate dehydrogenase activity in Purkinje cells of 9-weeks-old mutant mice indicating the electron transport chain dysfunction in mitochondria
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• do not display ataxia
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• shorter mean latency to fall in the first trial and performance improves only slightly over subsequent trials
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| N |
• do not display defects in cerebellar development
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• at P70, but not at P20, Purkinje cells show a decrease in firing frequency
• at P70 Purkinje cells show an increase in variability of firing
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice start showing problems righting themselves around P10-P12
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• mice start showing loss of balance during walking around P10-12
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• P18 mice perform worse on the rotarod than wild-type mice
• P30 mice are severely impaired on the rotarod, staying a shorter amount of time on the accelerating rod than wild-type mice, falling off the rod at a lower rotating speed, and do not improve over time
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• degeneration of molecular layer interneurons by P200-250
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• volume reductions and increase in surface density in all cerebellar nuclei
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• neurodegenerative changes are first seen around P45, with argyrophylic staining in the Purkinje cell layer
• Purkinje cell degeneration in the cerebellum is clearly seen from P60, showing somatic sprouting and axonal swellings and progresses until P200-P250 when a significant decrease in Purkinje cell number is seen
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• degeneration of granule cells by P200-250
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• neurodegenerative changes are first seen around P45, with argyrophylic staining in the molecular layer
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| cerebellar ataxia | DOID:0050753 | J:234599 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not exhibit motor dysfunction on the rotarod
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit impairment in vestibuloocular reflex in the dark decrease learning and dark, gain consolidation compared with wild-type mice
• mice exhibit impaired vestibuloocular reflex in the dark phase adjustment from day 4 (long-term memory consolidation) compared with wild-type mice
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• mice exhibit impairment in vestibuloocular reflex in the dark decrease learning and dark, gain consolidation compared with wild-type mice
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• mice exhibit decreased gain in optokinetic reflex compared with wild-type mice
• mice exhibit a phase lag during optokinetic reflex compared with wild-type mice
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• mice exhibit a phase lag during vestibuloocular reflex in the dark compared with wild-type mice
• mice exhibit impairment in vestibuloocular reflex in the dark decrease learning compared with wild-type mice
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• mice exhibit a phase lag during vestibuloocular reflex in the light compared with wild-type mice
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| N |
• mice exhibit normal cerebellar histology, synaptic morphology and synaptic function
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• mice exhibit reduced GABA-induced chloride ion currents compared with wild-type mice that is not as severe as in Slc12a5tm2.1Tjj/Slc12a5tm2.1Tjj Tg(Pcp2-cre)2Mpin mice
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• mice exhibit a phase lag during vestibuloocular reflex in the dark compared with wild-type mice
• mice exhibit impairment in vestibuloocular reflex in the dark decrease learning compared with wild-type mice
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• mice exhibit a phase lag during vestibuloocular reflex in the light compared with wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Neurodegenerative changes in Ercc6tm1Gvh/Ercc6tm1Gvh Xpatm1Gvh/Xpatm1Hvs Tg(Pcp2-cre)2Mpin/0 mice
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• argyrophilic axonal degeneration in the cerebellar white matter and cerebellar nuclei
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit dystonia that is more severe than in single Cacna1atg homozygotes
• more than 95% of abnormal movements are either tonic or clonic
• mice show a small (5%) but significant shift towards increased head/neck postures than in single Cacna1atg homozygotes
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• mice exhibit dystonia that is more severe than in single Cacna1atg homozygotes
• more than 95% of abnormal movements are either tonic or clonic
• mice show a small (5%) but significant shift towards increased head/neck postures than in single Cacna1atg homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• when the allele is inherited paternally, mice exhibit normal posture, righting response, motor coordination and balance
• when the allele is inherited paternally, mice do not exhibit significant myoclonus
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• when the allele is inherited paternally, mice exhibit impaired motor learning on a beam-walking test compared with control mice
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• activity, movement number and movement time when the allele is inherited paternally
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| N |
• when the allele is inherited paternally, Purkinje cells exhibit normal nuclear envelops
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• brain injections of rAAV8 virus expressing cre
• increase in overlaps of Purkinji Cell dendritic branches
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• dyskinesis is induced by stress or chemicals, such as a new environment, cage transport, short restraint, or administration of caffeine and alcohol
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• mice exhibit sustained axial dystonia and repetitive clonic limb movements unlike wild-type mice
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• mice exhibit stereotyped 6 to 7 spikes per second generalized spike-wave seizure discharges unlike wild-type mice
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• at P21, only 2 of 30 cells exhibit spontaneous action potential activity compared with wild-type cells
• at P48, Purkinje cells lack spontaneous action potential firing unlike wild-type cells
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• omegaAgalVA-treatment fails to reduced inhibitory postsynaptic current (IPSC) amplitudes unlike similarly treated wild-type mice
• however, response to omega CtxGVIA is normal
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• Purkinje cells exhibit reduced P/Q-type channel current density compared with wild-type cells
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• mice perform extremely poorly on a rotarod compared with wild-type mice
• mice exhibit impaired performance in incline and pole tests compared with wild-type mice
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• mice exhibit impaired coordination of forepaw grip compared with wild-type mice
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• dyskinesis is induced by stress or chemicals, such as a new environment, cage transport, short restraint, or administration of caffeine and alcohol
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• mice exhibit sustained axial dystonia and repetitive clonic limb movements unlike wild-type mice
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• mice exhibit stereotyped 6 to 7 spikes per second generalized spike-wave seizure discharges unlike wild-type mice
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• worsening with age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice show reduced investigation of social odors compared with controls, suggesting impaired discrimination of social olfactory cues
• however, mice show normal investigation of non-social olfactory cues
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• increase in self-grooming rates
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• mice show impaired male-female social interactions, with reductions in the time that mice spend interacting compared to controls
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• in a 3-chambered assay of social approach and preference for social novelty, mice exhibit social impairments, showing no differences between the time spend in the chamber or in interaction with the novel mouse versus the novel object unlike controls
• in a social novelty paradigm, mice show no preference for social novelty
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• P5-P12 pups show increased vocalizations
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• increase in spine density on Purkinje cell dendrites
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• Purkinje cell excitability is reduced, with Purkinje cells showing lower, graded spontaneous spiking rate, and current injection evokes fewer action potentials in Purkinje cells
• injection of small hyperpolarizing currents results in smaller voltage changes in Purkinje cells, indicating a decrease in the effective input resistance
• despite receiving normal functioning synaptic inputs, the output of the cerebellar cortex is reduced, both tonically and in response to incoming excitatory drive
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit similar acquisition learning of a submerged escape-platform location compared to controls, however when the escape platform location is reversed, mutants show impaired learning of the new platform location
• rapamycin treatment prevents the reversal learning impairment
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• mice show reduced investigation of social odors compared with controls, suggesting impaired discrimination of social olfactory cues
• however, mice show normal investigation of non-social olfactory cues
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• increase in self-grooming rates
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• mutants show initial signs of ataxia at 7-8 weeks of age which progresses with age
• mice show decreased stride length and increased stride width at 4 months of age
• rapamycin treated mutants do not show ataxic gait
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• mutants show impaired motor learning on the accelerating rotarod test before ataxia onset
• treatment with rapamycin prevents the motor phenotypes
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• mice show impaired male-female social interactions, with reductions in the time that mice spend interacting compared to controls
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• in a 3-chambered assay of social approach and preference for social novelty, mice show social impairments, showing no differences between the time spend in the chamber or in interaction with the novel mouse versus the novel object
• in a social novelty paradigm, mice show no preference for social novelty
• treatment with rapamycin results in normal social behavior
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• P5-P12 pups show increased vocalizations
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• cerebellar Purkinje cell layer is abnormal with increased soma area and reduced Purkinje cell numbers
• treatment with rapamycin starting at P7 prevents the Purkinje cell defects
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• Purkinje cell soma area is increased at 4 weeks of age
• markers for endoplasmic reticulum and oxidative stress are elevated indicating elevated neuronal stress of Purkinje cells
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• Purkinje cells display abnormal axonal projections with numerous protrusions and abnormal collateralization
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• increase in spine density on Purkinje cell dendrites
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• decrease in Purkinje cell numbers are first seen at 2 months of age, with a further reduction at 4 months
• an increase in Purkinje cell apoptosis is seen at 7-8 weeks of age
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• Purkinje cell excitability is reduced, with Purkinje cells showing lower, graded spontaneous spiking rate, and current injection evokes fewer action potentials in Purkinje cells
• injection of small hyperpolarizing currents results in smaller voltage changes in Purkinje cells, indicating a decrease in the effective input resistance
• despite receiving normal functioning synaptic inputs, the output of the cerebellar cortex is reduced, both tonically and in response to incoming excitatory drive
• however, alterations in synaptic transmission are not apparent in mutants
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| autism spectrum disorder | DOID:0060041 | J:186699 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Purkinje cell bodies are absent from the cerebellum
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• the percentage, amplitude, and velocity of conditioned responses were reduced in the 3rd and 4th training sessions; however the startle response was normal
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• the length of Purkinje cell spine heads and necks is increased
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• induction of long term depression in Purkinje cells is significantly enhanced when stimulating parallel fibers
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| fragile X syndrome | DOID:14261 |
OMIM:300624 |
J:101021 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced gain of the optokinetic reflex at all stimulus frequencies tested
• however, the phase values do not differ from controls
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• reduced gain of the vestibuloocular reflex in the light at all stimulus frequencies tested
• however, the phase values do not differ from controls and no difference was detected in this reflex in the dark
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• increase in the number of foot slips in a runway test even after prolonged training
• impaired ability to stay on a stationary bar
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| N |
• despite loss of expression in Purkinje cells no defect in long term depression is detected
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• following single shock parallel fiber activation early synaptic calcium transients are 2 to 3 times larger and their decay constants are 3 to 4 times shorter compared to controls
• following single shock activation of climbing fibers the amplitude of fast synaptic calcium transients is increased by about 80% and the decay time constant is reduced by greater than 50%
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• reduced gain of the vestibuloocular reflex in the light at all stimulus frequencies tested
• however, the phase values do not differ from controls and no difference was detected in this reflex in the dark
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• after 10 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Abnormal mitochondrial network in Afg3l2tm1Arte/Afg3l2tm1Arte Tg(Pcp2-cre)2Mpin/0 Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+ mice
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• at 4 weeks, Purkinje cells exhibit fragmentation of mitochondria unlike control cells
• at 6 weeks, mitochondrial fragmentation is very pronounced
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• at 4 weeks, Purkinje cells exhibit fragmentation of mitochondria unlike control cells
• at 6 weeks, mitochondrial fragmentation is very pronounced
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• Purkinje cell electrophysiological properties are normal at 4 to 5 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice have no motor disabilities, no ataxia or tremor and performed normally on a rotarod test
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• mice are resistant to zolpidem induced sedative and ataxic effects
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• miniature inhibitory postsynaptic currents are absent from all Purkinje cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal cerebellar histology, synaptic morphology and synaptic function
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• chloride ion concentration is increased 2-fold compared to in wild-type mice
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• GABA-induced hyperpolarization in Purkinje cells is nearly abolished compared to in wild-type cells
• regularity of Purkinje cell firing is reduced compared to in wild-type cells
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• regularity of Purkinje cell firing is reduced compared to in wild-type cells
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• GABA-induced hyperpolarization in Purkinje cells is nearly abolished compared to in wild-type cells
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• mice exhibit impairment in vestibuloocular reflex in the dark decrease learning and dark, gain consolidation compared with wild-type mice
• in a long-term vestibuloocular reflex in the dark phase reversal training paradigm, mice are unable to reverse the phase of their eye movements unlike wild-type mice
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• mice exhibit impairment in vestibuloocular reflex in the dark decrease learning and dark, gain consolidation compared with wild-type mice
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• mice exhibit decreased gain in optokinetic reflex compared with wild-type mice
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| N |
• mice exhibit normal retina function in vestibuloocular reflex adaptation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal GABA-induced chloride ion currents
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in vitro, spontaneous action potential firing frequency is significantly higher than that in control Purkinje cells when the inhibitory input is present; firing frequency of Purkinje cells remains significantly higher when both inhibitory and excitatory inputs are blocked in the presence of the GABAAR-blocker picrotoxin
• in vivo recordings showed a significant increase in simple spike firing frequency of Purkinje cells relative to those in wild-type mice
• however, both the level of regularity of simple spike firing and complex spike frequency remain normal
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• the amplitude of afterhyperpolarization is significantly smaller than that in control Purkinje cells
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• following application of the GABAAR agonist muscimol to proximal dendrites of Purkinje cells, the reversal potential of GABAA-current (EGABA) is significantly more hyperpolarized than in control Purkinje cells, as shown by a negative shift in EGABA
• however, the resting membrane potential is not significantly altered in Purkinje cells
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• the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) is significantly higher than that in control Purkinje cells
• no differences are noted in the maximum amplitude or in the rise and decay time of sIPSCs relative to control cells
• in vitro cell-attached recordings of molecular layer interneurons revealed normal firing frequency in presynaptic interneurons
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• perforated patch clamp recordings of Purkinje cells revealed a negative shift in the reversal potential of chloride as reflected in the GABAA-receptor evoked currents, indicating a decrease in intracellular chloride concentration; on average, [Cl-]i is 35% lower than that in control Purkinje cells
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| N |
• mice exhibit no detectable differences during performance or adaptation of compensatory eye movements relative to control mice
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• in the Erasmus Ladder paradigm, mice exhibit a significantly higher number of steps per session during both perturbed and non-perturbed (baseline) sessions
• mice show a higher % of small steps and a lower % of large steps than wild-type mice in all sessions
• however, the average step time is not significantly altered
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Purkinje cell degeneration in Afg3l2tm1Arte/Afg3l2tm1Arte Tg(Pcp2-cre)2Mpin/0 mice
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• impaired in Purkinje cells
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• progressive
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• progressive
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• at 4 weeks, Purkinje cells have swollen mitochondria with disrupted cristae unlike control cells
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• disappearance of almost all neurons at 12 weeks
• however, normal numbers at 4 weeks
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• postnatal and progressive
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• loss observed at 6 weeks and progresses over time
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• unsteady at 8 weeks
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• impaired in Purkinje cells
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• progressive
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• progressive
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• at 4 weeks, Purkinje cells have swollen mitochondria with disrupted cristae unlike control cells
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• progressive
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• progressive
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in the open field (OF) test, total distance moved is reduced by 40% and average speed is reduced by 39.6% relative to controls, whereas no differences are observed in the ratio of the distance moved in the center to the distance moved in the periphery, or in the ratio of time spent in the center to the time spent in the periphery
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• combined behavioral analysis of 8-weeks-old male mice using the rotarod test, open field test, CatWalk analysis, and elevated plus maze (EPM) indicate a characteristic bradykinesia with a reduction in spontaneous movements
• in the open field (OF) test, total distance moved is reduced by 40% and average speed is reduced by 39.6% relative to controls, whereas no significant differences are observed in the ratio of the distance moved in the center to the distance moved in the periphery, or in the ratio of time spent in the center to the time spent in the periphery
• CatWalk analysis shows that the base of support (BOS) between the hind paws is reduced by 34.8% and BOS between the front paws is reduced by 26.1% whereas inter-paw coordination is normal, indicating decreased amplitude of stepping; all of the paw print areas show a marked decline (approximately 58.1% for the left front paw, 60.4% for the left hind paw, 54.1% for the right front paw, and 44.7% for the right hind paw), confirming bradykinesia
• in the rotarod test, no significant difference is observed in the latency to fall relative to controls, indicating absence of ataxia and normal balance ability
• in the EPM test, no significant differences are observed in the duration or frequency in the central platform, in the closed arms, and in the open arms relative controls, suggesting that emotional behavior is largely unaffected
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• TEM analysis of PC mitochondria shows a significant increase in mitochondrial circularity relative to controls
• however, no significant change in PC mitochondrial density, area or perimeter is observed
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• electrical patch clamp recordings on freshly isolated 4/5 lobes of the cerebellar cortex show alterations in the properties of both spontaneous and evoked firings in PCs
• analysis of spontaneous action potential (AP) firings of PCs shows that the AP half-width is reduced by 19.7% while the rise and decay slope becomes steeper by 21.8% and 21.1%, respectively, relative to controls
• analysis of the evoked spikes of PCs shows that the proportion of active and inactive PCs is reduced by 5% relative to controls (68% vs 73%, respectively)
• however, the total firing number of active and inactive PCs is not significantly altered at any given current
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• TEM analysis of PC mitochondria shows a significant increase in mitochondrial circularity relative to controls
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• TEM analysis of PC mitochondria shows a significant increase in mitochondrial circularity relative to controls
• however, no significant change in PC mitochondrial density, area or perimeter is observed
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• microplate reader assays indicate that the mitochondrial membrane potential (MMP) level is increased by 28.86% while the ATP level is increased by 57.86% in isolated cerebellum tissue
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• reactive oxygen species (ROS) probe imaging shows that ROS generation is significantly increased in the molecular layer of cerebellar tissue
• a microplate reader assay indicates that ROS generation is increased by 27.08% in isolated cerebellum tissue
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N |
• 8-weeks-old male mice exhibit no hypotonia (a typical symptom of cerebellar disorders) by electromyogram recordings detection on the gastrocnemius muscle
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N |
• 8-weeks-old male mice exhibit no significant changes in average body length, ratio of head length to body length, and average body weight relative to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• extensive overlaps of Purkinje cell dendritic branches
• dendrites otherwise normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• treatment with zolpiderm does not produce sedation or overt ataxia
• sensitivity to zolpidem is only restored in Purkinje cells
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• following treatment with 3 mg/kg of zolpidem, mice exhibit reduced ability to stay on a rotating rod
• following treatment with zolpidem, mice need more time to cross a hanging beam than do untreated mice
• however, untreated mice have no motor disabilities, no ataxia or tremor and performed normally on a rotarod test and pre-treatment with flumazenil blocks the effects of zolpiderm
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• mice treated with zolpidem exhibit a raise the amplitude and increase the charge of miniature inhibitory postsynaptic currents (mIPSCs) indicating a restoration of zolpiderm-sensitivity but only in Purkinje cells
• due to mosaic expression of the transgene in female mice with integration into the X chromosome, some mice exhibit a lack of mIPSCsdue to mosaic expression of the transgene in female mice with integration into the X chromosome, some mice exhibit a lack of mIPSCs
• however, in GFP+ cells normal zolpidem-sensitivity is restored
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants are ataxic at 3 months of age
• treatment of mutants with rapamycin rescues the ataxic gait
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• mutants exhibit rotarod defects, falling off the rotarod sooner than controls
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• mutants take wider steps than control mice
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• Purkinje cells exhibit apoptotic cell death and increased ER and oxidative stress
• treatment of mutants with rapamycin rescues Purkinje cell death and alleviates ER stress
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• mutants progressively lose Purkinje cells beginning at one month of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| tuberous sclerosis | DOID:13515 |
OMIM:PS191100 |
J:174327 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 10% of mutants exhibit spontaneous deaths before weaning; cause of death is unknown
|
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• Purkinje cells are larger than in wild-type mice
|
|
• mutants exhibit Purkinje cell loss beginning at one month of age which becomes progressively more pronounced over time
• by 7 months of age, mutants lose more Purkinje cells than Tsc2tm1.1Mjg/Tsc2tm1.1Mjg Tg(Pcp2-cre)2Mpin/0 mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| tuberous sclerosis | DOID:13515 |
OMIM:PS191100 |
J:174327 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice show mildly increased anxiety-like behavior in the light-dark test
• however, mice show normal behavior in the elevated plus maze and in the center region of the open-field arena
|
|
|
• mice show impaired motor coordination in the Erasmus ladder test
• however, mice do not show any abnormalities in social interaction, social novelty recognition, ultrasonic vocalization, repetitive behaviors (self-grooming, jumping, digging, and marble burying), in the rotarod test, and open-field behavior and show normal visual and olfactory function
|
|
|
• mice show increased repetitive behavior in the hole-board test
|
|
• reduction in levels of excitatory synaptic protein (GluD2 and PSD-93) levels in the cerebellum
|
|
• Purkinje cells show miniature excitatory postsynaptic currents (mEPSCs) with reduced frequency but normal amplitude
• however, mice show normal LTD at parallel fibers-Purkinje cell synapses in the cerebellum
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal cerebellar foliation and lamination of cortical structures
|
|
• reduced number of vGluT2+ puncta in the cerebella
• climbing fiber terminals penetrate to a shallower depth than in wild-type mice
• however, transforming Purkinje cells with a wild-type form of the gene re-establishes climbing fiber synapse elimination
|
|
• reduced complex spikes from Purkinje cells
• reduced climbing fiber-evoked afterhyperpolarization and suppression of spontaneous spikes
|
|
• whole-cell patch-clamp recordings show reduced one-to-one relationship of Purkinje cells with climbing fibers and smaller amplitude of strongest climbing fiber excitatory postsynaptic currents
• however, transforming Purkinje cells with a wild-type form (but not one lacking a domain required for interaction with C1ql1) of the gene re-establishes increases amplitude of strongest climbing fiber excitatory postsynaptic currents
|
|
• simultaneously activating parallel fibers and climbing fibers for 2 min at 1 Hz in the current-clamp mode fails to develop long term depression
|
| N |
• mice exhibit no ataxia and normal motor coordination on the rotor-rod test
|
|
• severely impaired adaptation of the horizontal optokinetic response
• however, horizontal optokinetic response prior to training is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit an increase in voluntary activity level in the wheel-running test during the light phase, but no change during the dark phase; activity is especially high at 9 am and especially low during the 1st half of the active phase
• mice exhibit an increase in activity level during the rest (light) phase and during the active (dark) phase in the continuous open field
• however, mice show no difference in the latency to withdraw from the heat stimuli in the tail-flick test
|
|
• analysis of sleep-like behaviors indicates an increase in probability of waking in the rest phase, especially at 7 am, 8 am and the 2nd half of the rest phase, but not in the active phase
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| restless legs syndrome | DOID:0050425 |
OMIM:PS102300 |
J:298663 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced calcium buffering capacity in Purkinje cell mitochondria
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal amount and distribution of vGluT2 immunoreactivity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no change in parallel fiber synpatic transmission
• no change in basket/stellate cell synapse-mediated mIPSCs
|
|
• small decrease in climbing fiber synapse EPSC amplitude
• no change in paired pulse ratio is detected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no change in density, distribution or size of excitatory climbing-fiber synapses or inhibitory basket/stellate cell synapses
|
|
• 25% increase in climbing fiber synapse EPSC amplitude
|
|
• 50% reduction in IPSC amplitude
|
|
• 67% decrease in spontaneous mIPSC frequency, but no change in amplitude or kinetics
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• bouton size is reduced
|
|
• 50% decrease in density of climbing fiber synapse on distal Purkinje cell dendrites
• 15% decrease in density of climbing fiber synapse on proximal Purkinje cell dendrites
• inhibitory basket/stellate cell synapses are increased in size, but not number
• 25% decrease in size of climbing fiber synapse on distal and proximal Purkinje cell dendrites
• increase in puncta density as detected by GAD65
• parallel fiber synapse density is not altered
|
|
• decreased frequency of delayed quantal release events, but not amplitude events
• impaired synaptic transmission at GABAergic synapses
|
|
• 40% decrease in amplitude of climbing fiber EPSCs in juvenile and adult mice
• however, no change in kinetics or paired pulse ratio of climbing fiber EPSCs and no alterations in parallel-fiber EPSCs
|
|
• 80% decrease in IPSC amplitude in Purkinje cells, but no changes in kinetics or paired pulse ratio
|
|
• 80% decrease in mIPSC frequency and amplitude (45%) in basket/stellate cell synapses
• decrease in decay, but not rise times of mIPSCs
|
|
• 45% decrease in basket/stellate cell synapses
|
|
• 80% decrease in basket/stellate cell synapses
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no change in parallel fiber synpatic transmission
|
|
• slight decrease in climbing-fiber synapse (vGluT2 staining) cluster density and size
|
|
• decrease in climbing-fiber EPSC amplitude, but no change in quantal events
|
|
• large decrease in frequency (90%) and amplitude (45%) of mIPScs
|
|
• 45% decrease
|
|
• 90% decrease
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no change in parallel fiber synpatic transmission
• no change in basket/stellate cell synapse-mediated mIPSCs
|
|
• 5% loss of distal climbing-fiber synapse numbers
• 25% decrease in synapse size
|
|
• modest decrease (10%) in climbing fiber synapse EPSC amplitude
• no change in paired pulse ratio is detected or synapse elimination
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no change in parallel fiber synpatic transmission
• no change in basket/stellate cell synapse-mediated mIPSCs
|
|
• modest decrease (10%) in climbing fiber synapse EPSC amplitude
• no change in paired pulse ratio is detected
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice are hyperactive during open-field tests, showing increased total distance traveled and increased number of ambulatory episodes
• however, mice exhibit normal performance on the rotarod
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• minor
|
| N |
• mice exhibit normal nervous system morphology with no increase in DNA damage
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• born at expected Mendelian ratios
• survive to adulthood
|
| N |
• no seizure-like movements
|
|
• smaller amplitude of horizontal optico kinetic reflex gain but timing is normal
• no adaptive increase in horizontal optico kinetic reflex gain at 10 weeks after 1 hour of exposure to screen oscillations
|
| N |
• cerebellar morphology is more or less normal
• climbing fiber distribution is normal at 10 weeks of age
• no abnormal enlargement of parallel fiber presynaptic terminals
|
|
• fewer dendritic branching points
• increased spine density in the distal dendritic region
|
|
• soma is smaller at 10 weeks of age but no degeneration is apparent
|
|
• thin at 10 weeks of age
|
|
• significantly increased parallel fiber EPSP at 10 weeks of age
|
|
• induction of long term depression by stimulation of parallel fibers and climbing fibers is blocked
• long term depression by direct depolarization of Purkinje cells is blocked
|
|
• smaller amplitude of horizontal optico kinetic reflex gain but timing is normal
• no adaptive increase in horizontal optico kinetic reflex gain at 10 weeks after 1 hour of exposure to screen oscillations
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• percentage of purkinje fibers synapsing with parallel fibers is normal
|
|
• distal spine density is 143% of controls
• spine lengths are greater
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• long term depression in the cerebellum is suppressed
• motor coordination as determined by footprint, runway, and rotarod tests was normal
• less vestibulo-occular reflex adaptation than in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• transgenic mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 01/28/2026 MGI 6.24 |
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