Analysis Tools|
Allele Symbol Allele Name Allele ID |
Slc6a3tm1(cre)Xz targeted mutation 1, Xiaoxi Zhuang MGI:3691571 |
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| Summary |
13 genotypes
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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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• resistant to agonist U50,488-induced conditioned place aversion (CPA)
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• evoked dopamine response is not inhibited, in contrast to inhibition of dopamine in controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice lack the NMDAR component of the excitatory postsynaptic current (EPSC) in dopaminergic neurons unlike in wild-type mice
• AMPA-evoked EPSCs are increased compared to wild-type mice
• however, NMDAR-mediated EPSCs in non-dopaminergic neurons are normal
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• absent in dopaminergic neurons
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• miniature excitatory postsynaptic current (EPSC) are increased in amplitude and frequency compared to in similarly treated wild-type mice that is identical to the increase observed in mice treated with cocaine
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• 21 days after cocaine withdrawal mice fail to exhibit significant enhancement of behavioral sensitization
• however, mice exhibit normal locomotor-stimulating effects of drugs
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• mice fail to exhibit conditioned place preference for cocaine
• however, mice exhibit normal conditioned place aversion to naloxone
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• late-onset, progressive
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• deficits in elicited dopamine release
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not exhibit any dopaminergic neuron loss the substantia nigra pars compacta and ventral tegmental area
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adults are modestly but significantly less active than heterozygous controls; total ambulations during a 1 hour observation session are lower in conditional null mice
• mice exhibit normal rearing behavior but travel less in the field periphery and make fewer entries into center compared to controls
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| N |
• although Ret expression is lost, in adults the total cell counts and size of dopaminergic neurons, TH-positive fiber density in the striatum and nucleus accumbens, nigrostriatal and ventral tegmental area pathways, and levels of dopamine and its metabolites, are all similar to wild-type
• mice do not appear to have sensorimotor deficits with the modest decrease in locomotor activity
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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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• at about 18 months
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• in the the substantia nigra pars compacta at 4, 8 and 16 months
• in the ventral tegmental area at 16 months
• in the striatum at 14 months
• non cell-autonomous
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• in striatal TH+ fiber density at 12 months
• in ChAT+ neurons in the striatum at 6 months
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• in striatal TH+ fiber density at 8 months
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• impaired amphetamine elicited
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• mice exhibit increased gait length coefficient of variability at 10 months of age, and shortened time allotted for braking in each stride and increased paw angle at 11 months of age compared with wild-type mice
• however, treatment with L-DOPA and THP normalizes increased variability in stride length, THP normalizes brake stride ratio and treatment with L-DOPA normalizes alterations in paw angles
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• at 2 to 5 months
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• at 7 to 12 months
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• rapidly deteriorating locomotion activity leading to pelvic dragging followed by partial hindlimb paralysis at about 18 months
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• in the ventral midbrain at 16 months
• in the striatum at 2 and 16 months
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• in the ventral midbrain at 2 months
• in the striatum at 7 months
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• performance on the rotarod is similar to controls, although there is a slight trend toward improved performance
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• resistant to agonist U50,488-induced conditioned place aversion (CPA)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are more active during the wake cycle than controls at 7 months of age but this difference is no longer significant at 12 months of age
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• mice exhibit an age dependent decrease in striatal dopamine content in the brain, with a 55.5% reduction by 7-9 months of age compared to controls
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• 40% loss of substantia nigra pars compacta dopamine neurons by 7-9 months of age
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• neuronal inclusions are present in the substantia nigra pars compacta
• inclusions are often perinuclear but are also in the neuropil and are positive for ubiquitin
• neuronal inclusions are present in juveniles but are smaller in size than at older ages
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• 40% loss of substantia nigra pars compacta dopamine neurons by 7-9 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Parkinson's disease | DOID:14330 |
OMIM:PS168600 |
J:192452 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit increased sensitivity to nicotine-induced locomotor depression compared with similarly treated wild-type mice
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• mice exhibit decreased place preference associated with nicotine compared with wild-type mice
• however, place preference associated with cocaine is normal
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• mice exhibit decreased place preference associated with nicotine compared with wild-type mice
• mice are insensitive to the anxiolytic effects of nicotine unlike wild-type mice
• however, mice exhibit normal nicotine-induced hypothermia
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• alpha-CtxMII-resistant dopamine release is abolished at low and moderate nicotine concentrations compared to in similarly treated wild-type neurons
• alpha-CtxMII-sensitive dopamine release is reduced at low levels of nicotine compared to in similarly treated wild-type neurons
• however, neurons exhibit normal alpha-CtxMII-sensitive dopamine release at moderate concentrations of nicotine and nicotine-stimulated GABA release from the cortex
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• only a minority of dopaminergic projections remain intake
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• YFP+ dopamine neurons fail to exhibit glutamatergic excitatory postsynaptic currents (EPSCs) unlike control cells
• at P9 to P10, mice exhibit a reduction in glutamatergic with fewer neurons responding to ventral tegmental area stimulation compared with similarly treated control cells
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• cocaine-treated mice exhibit less locomotor activity compared with control mice
• however, cocaine-treated mice exhibit conditioned place preference
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• the ventral striatum exhibit reduced dopamine and evoked dopamine release compared to in control mice
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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 11/12/2024 MGI 6.24 |
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