All Phenotypes Slc6a3<tm1(cre)Xz> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Slc6a3^tm1(cre)Xz
targeted mutation 1, Xiaoxi Zhuang
MGI:3691571

Summary

13 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129S1/Sv	MGI:5285627
ht2	Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129S1/Sv * C57BL/6 * SJL	MGI:3691579
cn3	Oprk1^tm2.1Kff/Oprk1^tm2.1Kff Slc6a3^tm1(cre)Xz/0	involves: 129 * 129S1/Sv * C57BL/6	MGI:5824892
cn4	Grin1^tm1Rpa/Grin1^tm1.1Rpa Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129S1/Sv	MGI:3835418
cn5	Ret^tm1Kln/Ret^tm1Kln Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129S1/Sv	MGI:5440833
cn6	Smo^tm2Amc/Smo^tm2Amc Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129S1/Sv * 129X1/SvJ	MGI:5440832
cn7	Ret^tm13.1Jmi/Ret^tm13Jmi Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129S1/Sv * 129X1/SvJ	MGI:3692551
cn8	Rpl22^tm1.1Psam/Rpl22⁺ Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129S1/Sv * 129X1/SvJ	MGI:4355970
cn9	Shh^tm1Ahk/Shh^tm1Ahk Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129S1/Sv * C57BL/6	MGI:5440834
cn10	Mapk14^tm1.1Otsu/Mapk14^tm1.2Otsu Slc6a3^tm1(cre)Xz/0	involves: 129S1/Sv * C57BL/6	MGI:5824896
cn11	Atg7^tm1Tchi/Atg7^tm1Tchi Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129S1/Sv * C57BL/6NCrlj * CBA/JNCrlj	MGI:5471365
cn12	Chrna4^tm1.1Tmcg/Chrna4^tm1.1Tmcg Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129S/SvEv * 129S1/Sv * C57BL/6	MGI:5285626
cn13	Slc17a6^tm1.1Thna/Slc17a6^tm1.1Thna Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺ Slc6a3^tm1(cre)Xz/Slc6a3⁺	involves: 129/Sv * 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6J	MGI:4879095

Allelic Composition	Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129S1/Sv

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Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

hyperactivity ( J:174505 )

Allelic Composition	Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129S1/Sv * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

normal phenotype

no abnormal phenotype detected ( J:115426 )

• mice are viable and fertile

Allelic Composition	Oprk1^tm2.1Kff/Oprk1^tm2.1Kff Slc6a3^tm1(cre)Xz/0
Genetic Background	involves: 129 * 129S1/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Oprk1^tm2.1Kff mutation (1 available); any Oprk1 mutation (29 available)
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

abnormal associative learning ( J:226396 )

• resistant to agonist U50,488-induced conditioned place aversion (CPA)

nervous system

abnormal synaptic dopamine release ( J:226396 )

• evoked dopamine response is not inhibited, in contrast to inhibition of dopamine in controls

Allelic Composition	Grin1^tm1Rpa/Grin1^tm1.1Rpa Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129S1/Sv

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Grin1^tm1.1Rpa mutation (0 available); any Grin1 mutation (64 available)
Grin1^tm1Rpa mutation (0 available); any Grin1 mutation (64 available)
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

abnormal excitatory postsynaptic currents ( J:145468 )

• 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

reduced long-term potentiation ( J:145468 )

• absent in dopaminergic neurons

abnormal miniature excitatory postsynaptic currents ( J:145468 )

• 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

increased miniature excitatory postsynaptic current amplitude ( J:145468 )

increased miniature excitatory postsynaptic current frequency ( J:145468 )

behavior/neurological

abnormal behavioral response to addictive substance ( J:145468 )

• 21 days after cocaine withdrawal mice fail to exhibit significant enhancement of behavioral sensitization

• however, mice exhibit normal locomotor-stimulating effects of drugs

impaired conditioned place preference behavior ( J:145468 )

• mice fail to exhibit conditioned place preference for cocaine

• however, mice exhibit normal conditioned place aversion to naloxone

Allelic Composition	Ret^tm1Kln/Ret^tm1Kln Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129S1/Sv

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ret^tm1Kln mutation (1 available); any Ret mutation (53 available)
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

loss of dopaminergic neurons ( J:188348 )

• late-onset, progressive

abnormal synaptic dopamine release ( J:188348 )

• deficits in elicited dopamine release

Allelic Composition	Smo^tm2Amc/Smo^tm2Amc Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)
Smo^tm2Amc mutation (1 available); any Smo mutation (39 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

nervous system phenotype ( J:188348 )

N	• mice do not exhibit any dopaminergic neuron loss the substantia nigra pars compacta and ventral tegmental area

Allelic Composition	Ret^tm13.1Jmi/Ret^tm13Jmi Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ret^tm13.1Jmi mutation (1 available); any Ret mutation (53 available)
Ret^tm13Jmi mutation (1 available); any Ret mutation (53 available)
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

decreased locomotor activity ( J:114682 )

• 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

nervous system

nervous system phenotype ( J:114682 )

• 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

Allelic Composition	Rpl22^tm1.1Psam/Rpl22⁺ Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rpl22^tm1.1Psam mutation (2 available); any Rpl22 mutation (46 available)
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

normal phenotype

no abnormal phenotype detected ( J:151962 )

Allelic Composition	Shh^tm1Ahk/Shh^tm1Ahk Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129S1/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shh^tm1Ahk mutation (0 available); any Shh mutation (45 available)
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:188348 )

• at about 18 months

nervous system

loss of dopaminergic neurons ( J:188348 )

• 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

decreased neuron number ( J:188348 )

• in striatal TH+ fiber density at 12 months

• in ChAT+ neurons in the striatum at 6 months

increased neuron number ( J:188348 )

• in striatal TH+ fiber density at 8 months

abnormal synaptic dopamine release ( J:188348 )

• impaired amphetamine elicited

behavior/neurological

abnormal gait ( J:188348 )

• 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

decreased locomotor activity ( J:188348 )

• at 2 to 5 months

hyperactivity ( J:188348 )

• at 7 to 12 months

hindlimb paralysis ( J:188348 )

• rapidly deteriorating locomotion activity leading to pelvic dragging followed by partial hindlimb paralysis at about 18 months

homeostasis/metabolism

decreased dopamine level ( J:188348 )

• in the ventral midbrain at 16 months

• in the striatum at 2 and 16 months

increased dopamine level ( J:188348 )

• in the ventral midbrain at 2 months

• in the striatum at 7 months

Allelic Composition	Mapk14^tm1.1Otsu/Mapk14^tm1.2Otsu Slc6a3^tm1(cre)Xz/0
Genetic Background	involves: 129S1/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mapk14^tm1.1Otsu mutation (0 available); any Mapk14 mutation (41 available)
Mapk14^tm1.2Otsu mutation (1 available); any Mapk14 mutation (41 available)
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

behavior/neurological phenotype ( J:226396 )

N	• performance on the rotarod is similar to controls, although there is a slight trend toward improved performance

abnormal associative learning ( J:226396 )

• resistant to agonist U50,488-induced conditioned place aversion (CPA)

Allelic Composition	Atg7^tm1Tchi/Atg7^tm1Tchi Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129S1/Sv * C57BL/6NCrlj * CBA/JNCrlj

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Atg7^tm1Tchi mutation (3 available); any Atg7 mutation (51 available)
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

hyperactivity ( J:192452 )

• 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

homeostasis/metabolism

decreased dopamine level ( J:192452 )

• 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

nervous system

abnormal substantia nigra pars compacta morphology ( J:192452 )

• 40% loss of substantia nigra pars compacta dopamine neurons by 7-9 months of age

abnormal neuron morphology ( J:192452 )

• 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

neuron degeneration ( J:192452 )

• 40% loss of substantia nigra pars compacta dopamine neurons by 7-9 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:192452

Allelic Composition	Chrna4^tm1.1Tmcg/Chrna4^tm1.1Tmcg Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129S/SvEv * 129S1/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Chrna4^tm1.1Tmcg mutation (0 available); any Chrna4 mutation (42 available)
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

enhanced behavioral response to nicotine ( J:174505 )

• mice exhibit increased sensitivity to nicotine-induced locomotor depression compared with similarly treated wild-type mice

impaired behavioral response to nicotine ( J:174505 )

• mice exhibit decreased place preference associated with nicotine compared with wild-type mice

• however, place preference associated with cocaine is normal

impaired conditioned place preference behavior ( J:174505 )

• 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

nervous system

abnormal synaptic dopamine release ( J:174505 )

• 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

Allelic Composition	Slc17a6^tm1.1Thna/Slc17a6^tm1.1Thna Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺ Slc6a3^tm1(cre)Xz/Slc6a3⁺
Genetic Background	involves: 129/Sv * 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sor^tm1(EYFP)Cos mutation (11 available); any Gt(ROSA)26Sor mutation (942 available)
Slc17a6^tm1.1Thna mutation (0 available); any Slc17a6 mutation (59 available)
Slc6a3^tm1(cre)Xz mutation (2 available); any Slc6a3 mutation (66 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

abnormal dopaminergic neuron morphology ( J:167767 )

• only a minority of dopaminergic projections remain intake

abnormal excitatory postsynaptic currents ( J:167767 )

• 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

behavior/neurological

impaired behavioral response to cocaine ( J:167767 )

• cocaine-treated mice exhibit less locomotor activity compared with control mice

• however, cocaine-treated mice exhibit conditioned place preference

homeostasis/metabolism

decreased dopamine level ( J:167767 )

• the ventral striatum exhibit reduced dopamine and evoked dopamine release compared to in control mice

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