Analysis Tools|
Allele Symbol Allele Name Allele ID |
Slc6a3+ wild type MGI:2430385 |
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| Summary |
37 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• blunted locomotor response to a moderate dose of amphetamine
• however, mice exhibit normal amphetamine-induced stereotypic behavior and SKF-38393-induced grooming
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• increased novelty-induced hyperlocomotion
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Data Sources
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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IMPC - JAX
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IMPC - JAX
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IMPC - JAX
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IMPC - JAX
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IMPC - JAX
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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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• mice show a reduction in vertical activity in both number of rearing events and time spent rearing
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• blunted locomotor response to a moderate dose of amphetamine
• reduced amphetamine-induced stereotypic behavior
• however, SKF-38393-induced grooming response is preserved
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• at baseline and in response to novelty
• however, habituation is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in DT-treated mice
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• mice injected intramuscularly with diphtheria toxin (DT) exhibit reduced dopamine levels in the striatum
• DT-treated mice exhibit reduced 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the striatum
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• locomotor activity is increased 1.4-fold at low doses in cocaine-treated mice unlike in similarly treated control mice
• at higher doses, cocaine-induced hyperactivity is 3.8-fold compared to 2.8-fold in similarly treated control mice
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• mice exhibit increased motivation to work for food compared with control mice
• however, mice exhibit normal profile of loss of responding following cessation of reward delivery
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• in an open field that is insensitive to quinpirole treatment
• however, habituation is normal
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• locomotor activity is increased 1.4-fold at low doses in cocaine-treated mice unlike in similarly treated control mice
• at higher doses, cocaine-induced hyperactivity is 3.8-fold compared to 2.8-fold in similarly treated control mice
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• quinpirole fails to induce a slow hyperpolarizing current in dopaminergic neurons unlike in similarly treated control cells
• however, response to baclofen is normal
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• decreased and insensitive to sulpiride
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• during train stimulation, mice exhibit supramaximal dopamine release that increases during stimulation that is insensitive to sulpiride unlike in control mice
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• quinpirole fails to induce a slow hyperpolarizing current in dopaminergic neurons or reduce locomotor activity unlike in similarly treated control mice
• sulpiride fails to decreased inhibitory postsynaptic currents unlike in control cells
• tyrosine hydroxylase activity is insensitive to quinpirole unlike in control cells
• however, response to baclofen is normal
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• mice treated with haloperidol exhibit greater decrease in locomotion compared with similarly treated control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice show no abnormal phenotype up to 1 year of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants die around 6-7 weeks of age due to malnutrition; this is most likely due to difficulty accessing food and water in normal cages due to a rearing defect
• however, when mutants are supplied with hydrated gel packs and crushed pieces of regular chow, all mutants survive beyond 6 months of age, with a majority surviving past 1 year of age
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• mutants are significantly smaller than controls by 5 weeks of age
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• mutants do not gain weight after 4 weeks of age
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• mutants are hunched by 5 weeks of age
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• severe rearing defect as early as 4 weeks of age
• treatment of mutants with L-DOPA alleviates the motor defects
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• mutants are hypoactive by 5 weeks of age
• at 4-5 weeks of age, mutants travel only 68% of the distance traveled by wild-type mice and by 8-11 weeks of age, the distance traveled reduces to 34% of wild-type, indicating an age-dependent decline in locomotive activity
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• beginning at 4-5 weeks, mutants exhibit progressive bradykinesia
• mutants exhibit a decline in the speed of movement with age compared to controls
• mutants spend twice as much time inactive at 6-7 weeks of age as controls and by 8-11 weeks of age, this increases to 6-fold increase in inactive time
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• loss of dopaminergic terminals in the striatum, with a 25% reduction in dopaminergic terminals at 3 weeks of age and 76% reduction by 8-10 weeks
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• mutants exhibit loss of dopaminergic efferents to the striatum, with a 25% reduction in dopaminergic terminals at 3 weeks of age and a 76% reduction by 8-10 weeks of age
• however, projections to the nucleus accumbens and olfactory tubercle are protected and the dopaminergic terminals are moderately preserved at 11-14 weeks
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• dopaminergic neurons remaining have smaller cell bodies and diminished neuronal processes
• dopaminergic neurons exhibit mitochondrial fragmentation and depletion
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• retrograde degeneration of substantia nigra pars compacta dopaminergic neurons and to a lesser extent in the mesolimbic pathway
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• progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit, with neuronal loss first seen at 10-12 weeks, when a 52% decrease in TH-positive neurons is seen
• some degeneration is also seen in the mesolimbic pathway, although a lesser extent than in the nigrostriatal circuit
• degeneration of dopaminergic neurons occurs in a stepwise manner, with initial defects at the axon terminals, followed 1-2 months later by degeneration of the cell bodies
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• mutants show decreased mitochondrial transport along nerve processes
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• dopaminergic neurons exhibit mitochondrial fragmentation and depletion
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Parkinson's disease | DOID:14330 |
OMIM:PS168600 |
J:188347 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• MPTP-treated mice exhibit reduced numbers of tyrosine hydroxylase (TH)+ neurons and GFP+ TH+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with similarly treated wild-type mice
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• the percentage of GFP+ glyco-Slc6a3 (DAT)+ neurons is higher than in control mice
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• MPTP-treated mice exhibit reduced numbers of tyrosine hydroxylase (TH)+ neurons and GFP+ TH+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with similarly treated wild-type mice
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• MPTP-treated mice exhibit reduced numbers of tyrosine hydroxylase (TH)+ neurons and GFP+ TH+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with similarly treated wild-type mice
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• the percentage of GFP+ glyco-Slc6a3 (DAT)+ neurons is higher than in control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• MPTP-treated mice exhibit increased number of tyrosine hydroxylase (TH)+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
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• mice exhibit a reduction in the percentage of Kcnj6 (Girk2)+ or glyco-Slc6a3 (DAT)+ and tyrosine hydroxylase (TH)+ neurons in the ventral tegmental area (VTA) compared with wild-type mice
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• MPTP-treated mice exhibit increased number of tyrosine hydroxylase (TH)+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
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• MPTP-treated mice exhibit increased number of tyrosine hydroxylase (TH)+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• MPTP-treated mice exhibit increased number of tyrosine hydroxylase (TH)+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
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• mice exhibit a reduction in the percentage of Kcnj6 (Girk2)+ or glyco-Slc6a3 (DAT)+ and tyrosine hydroxylase (TH)+ neurons in the ventral tegmental area (VTA) compared with wild-type mice
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• MPTP-treated mice exhibit increased number of tyrosine hydroxylase (TH)+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
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• MPTP-treated mice exhibit increased number of tyrosine hydroxylase (TH)+ neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• MPTP-treated mice exhibit a modest increased number of tyrosine hydroxylase (TH)+ in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
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• MPTP-treated mice exhibit a modest increased number of tyrosine hydroxylase (TH)+ in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
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• MPTP-treated mice exhibit a modest increased number of tyrosine hydroxylase (TH)+ in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) compared with Slc6a3tm1.1(cre)Bkmn heterozygotes
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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 |
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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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• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells
• however, mitochondria in the distal dopamine axons are morphologically spared
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• neurons exhibit less intense staining with a retrograde tracer (fluorogold) suggesting impaired retrograde transport and/or uptake of the tracer compared with control cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• triple mutants show same phenotype as Tfamtm1Lrsn, Slc6a3tm1(cre)Lrsn mice; neuronal inclusions remain indicating that additional lack of Snca is not required for develoment of the Parkonsonian phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• novel object recognition test indicates impaired short-term memory formation in adult and aged mice
• however, no differences are seen in anxiety or depression-like tests
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• impaired motor coordination in the pole test at 6 months of age and in the beam traversal and pole test at 18 months of age
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• in the open field, mice show a modest increase in locomotor activity at 18, but not 6, months of age
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• midbrain dopamine neuron innervation is impaired
• treatment with rapamycin almost completely normalizes the reduced striatal TH innervation
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• 3 month old mice exhibit abnormal nerve terminals in the striatum, with a 50% reduction in the density of TH-positive nerve terminals and abnormally large nerve terminals that reach up to 22 um in diameter frequently throughout the dorsal and ventral striatum
• enlarged presynaptic boutons show fewer synaptic vesicles at active zones and are filled with vacuoles and multilamellar autophagic-lysosomal vesicles that sometimes contain mitochondria
• 23% lower occurrence of synaptic active zones
• treatment with rapamycin alleviates the occurrence of abnormally large TH+ boutons in the striatum
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• synaptic morphology is disrupted in presynaptic midbrain dopamine neuron terminals
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• enlarged presynaptic boutons show fewer synaptic vesicles at active zones
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• progressive loss of TH-positive neurons in the ventral midbrain, with degenerating TH+ neurons frequently seen in young mice; reduction is seen within both the dorsal and ventral striatum
• dopamine transporter (DAT) expression is reduced, showing a modest reduction in young mice but a significant reduction in aged mice, indicating dopaminergic neuron degeneration
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• mice exhibit enhanced induced LTP of Shaffer collateral-CA1 pyramidal cell synapses
• however, basal synaptic transmission is normal
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• social olfaction is impaired in adult (6 months) and aged (18 months) mice
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• accumulation of lysosomes in axonal terminals of midbrain dopamine neurons
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• accumulation of autophagosomes in axonal terminals of midbrain dopamine neurons
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• the number of lipofuscin granules are reduced in midbrain dopamine neurons
• accumulation of electron-dense protein aggregates in midbrain dopamine neuron cell bodies
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• accumulation of autophagosomes in axonal terminals of midbrain dopamine neurons
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• dopamine and its metabolites are reduced in brain areas such as prefrontal cortex, hippocampus, dorsal striatum, nucleus accumbens, substantia nigra and the ventral tegmental area
• however, levels are not reduced in the olfactory bulb or the cerebellum
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Parkinson's disease | DOID:14330 |
OMIM:PS168600 |
J:222854 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• die before 7 weeks of age with a median survival of 5.8 weeks
• life span can be increased to 11-12 weeks of age when provided with moist food on the cage floor
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• pathological alterations (irregular margins and elongated nuclei) of the somata of the substantia nigra pars compacta are seen at 5 weeks of age
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• profound lack of dopaminergic neuron innervation in the striatum
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• severe respiratory chain deficiency in mitochondria in dopaminergic neurons
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• at 5 weeks of age
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• continue to lose weight even when provided with moist food on the cage floor
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• total distance traveled is significantly increased in an open field test
• however, locomotion as assessed by horizontal beam breaks is similar to controls
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• decreased rearing activity in an open field test
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• become severely hypokinetic with age
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• severe respiratory chain deficiency in mitochondria in dopaminergic neurons
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• severe reduction in the striatum at 5 weeks of age
• also reduced in the substantia nigra pars compacta
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• in the striatum
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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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• viable with normal locomotor activity and body weight
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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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• profound reduction in the number of labeled mitochondria in the dorsal striatum
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• mitochondria are spherical and enlarged with disorganized cristae
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• mitochondria in dopaminergic neurons are spherical and enlarged with disorganized cristae
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• profound reduction in the number of labeled mitochondria in the dorsal striatum
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• mitochondria in dopaminergic neurons are spherical and enlarged with disorganized cristae
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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 |
Mitochondria abnormalities in Tfamtm1Lrsn/Tfamtm1Lrsn Slc6a3tm1(cre)Lrsn/Slc6a3+ Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+ neurons
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• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells
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• smaller mitochondrial and the largest aggregates in a rare number of neurons exhibit reduced import competence compared with mitochondria in control cells
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• impaired from 20 weeks of age
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• from 20 weeks of age
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• rigidity from 20 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants have to be terminated at ~45 weeks due to poor general condition
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• mice aged 14-15 weeks display decreased exploratory activity
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• progressive Parkinsonian symptoms are observed, with tremor observed at 20 weeks of age
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• apparent limb rigidity is observed at 20 weeks of age
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• majority of neurons contain small cytoplasmic aggregates, detected at 6 weeks through 43 weeks
• inclusions are present in most dopaminergic midbrain neurons and the mean size increased as the neurodegeneration progressed
• large, partially electron-dense bodies located in dendritic structures close to neuronal somata are observed at 11 weeks; some of these bodies have an amorphous content with a diffuse lining, while others display tubular formations and have distinct double layer membranes which are ultrastructurally typical of mitochondrial membranes
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• dopaminergic (DA) neuron loss is observed in the dorsolateral striatum at 12 weeks of age, progressing to involve most of the dorsal and ventral striatum with age
• tyrosine hydroxylase-expressing midbrain neurons show a slow progressive cell loss, which is more marked and starts sooner in the substantia nigra compared to the ventral tegmental area
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• twitching is observed at 20 weeks of age
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• neuron loss results in loss of dopamine in the nigrostriatal system in 20-week old mice
• there are markedly increased ratios of dopamine metabolites to dopamine in the striatum at 20 weeks
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Parkinson's disease | DOID:14330 |
OMIM:PS168600 |
J:119515 | |
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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 |
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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 |
Altered dopamine neurons in the ventral midbrain of Ptentm1Hwu/Ptentm1Hwu Slc6a3tm1.1(cre)Bkmn/Slc6a3+ mice
| N |
• no difference in locomotor activity is seen compared to controls during exposure to a novel environment
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• mutants exhibit a significant reduction in ipsilateral rotational behavior in response to amphetamine administration after 6OHDA lesioning
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• neuronal hypertrophy in the ventral midbrain resulting in enlargement of the ventral midbrain area
• increase in the number of TH positive neurons in the substantia nigra compacta and ventral tegmental area of the adult ventral midbrain and an increase in neuronal soma size
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• increase in the number of TH positive neurons in the substantia nigra compacta
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• increase in the number of dopaminergic neuron dendritic processes in the substantia nigra pars reticulata
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• modest but significant enlargement of the caudal striatum
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• increase in number of dopaminergic neurons and fibers in the ventral mesencephalon
• dopaminergic neurons in the ventral midbrain are larger in size and have an increase in the number of dendritic processes in the substantia nigra pars reticulata
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• hypertrophy of dopamine neurons
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• mutant dopamine neurons are protected from 6OHDA induced lesions, fiber loss, and axonal loss in the striatum compared to controls
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• increase in total dopamine tissue levels in the dorsal striatum and midbrain, however, no alterations in basal dopamine extracellular levels or evoked dopamine release in the dorsal striatum
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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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice show decreased immobility time in the forced swimming test
• however, locomotor activity in the open field is normal and mice show normal general behaviors such as gait posture
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• dopamine and baclofen both fail to cause currents in single putative dopamine neurons from the ventral tegmental area
• however, glutamic acid causes currents to the same extent as that in VTA neurons from controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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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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• levels of dopamine and its metabolites (DOPA and HVA) are decreased by 54% in 7-11 month old mice in striatal tissue
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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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants at 2 months of age exhibit a decrease in the exploration time in the activity cage, with this reduction lasting the duration of the dark cycle
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• at 4 months of age, mutants exhibit an increased latency time to descend a pole from a fixed height, indicating poor motor coordination
• however, mutants show normal rotarod performance
• 4 month of mutants treated with L-DOPA and carbidopa, a common therapy for Parkinson Disease, exhibit improved performance on the pole test and the activity cage
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• mutants gain weight at a slower rate than controls; this slower weight gain is first observed at 2 months of age
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• mutants show a significant reduction in overall all amount of dopamine at both 4 and 12 months of age compared to controls
• mutants however show an increase in the amount of HVA and DOPA, downstream metabolites of dopamine, indicating altered dopamine metabolism in the striatum
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• mutants over 12 months of age exhibit an increase in monoamine neurotransmitters, noradrenaline and serotonin
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• mutants over 12 months of age exhibit an increase in monoamine neurotransmitters, noradrenaline and serotonin
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• at 9 months of age, but not 4 months, mutants exhibit a 60% reduction in TH+ neurons in the substantia nigra, and by 12 months of age, very few TH+ neurons are left in the substantia nigra
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• mutants exhibit a reduction in TH+ neurons in the striatum at 4 months of age
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• mutants exhibit a reduction in dopamine transporter steady-state levels in the striatum, indicating a reduction of dopaminergic presynaptic terminals in the striatum at 4 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:178139 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increased spontaneous locomotor activity
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increased spontaneous locomotor activity
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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 03/18/2025 MGI 6.24 |
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