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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Slc6a3tm1.1(cre)Bkmn
targeted mutation 1.1, Cristina M Backman
MGI:3689434
Summary 11 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Slc6a3tm1.1(cre)Bkmn/Slc6a3tm1.1(cre)Bkmn involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:3689567
cn2
Cox10tm1Ctm/Cox10tm1Ctm
Slc6a3tm1.1(cre)Bkmn/?
B6.Cg-Cox10tm1Ctm Slc6a3tm1.1(cre)Bkmn MGI:5775427
cn3
Drd2tm1.1Mrub/Drd2tm1.1Mrub
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
B6.Cg-Drd2tm1.1Mrub Slc6a3tm1.1(cre)Bkmn MGI:5292386
cn4
Gt(ROSA)26Sortm1.1(CAG-COX8A/Dendra2)Dcc/Gt(ROSA)26Sor+
Mfn1tm2Dcc/Mfn1tm2Dcc
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
involves: 129 * 129S6/SvEvTac * C57BL/6J * SJL/J MGI:5441518
cn5
Gt(ROSA)26Sortm1.1(CAG-COX8A/Dendra2)Dcc/Gt(ROSA)26Sor+
Mfn2tm3Dcc/Mfn2tm3Dcc
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
involves: 129 * 129S6/SvEvTac * C57BL/6J * SJL/J MGI:5441517
cn6
Otx2tm6Asim/Otx2tm11Asim
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ MGI:4887467
cn7
Gt(ROSA)26Sortm1.1(Otx2)Daac/Gt(ROSA)26Sortm1.1(Otx2)Daac
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
Tg(CAG-Otx2,-GFP)21Asim/0
involves: 129P2/OlaHsd * C57BL/6 * DBA/2 MGI:4887466
cn8
Gt(ROSA)26Sortm1.1(Otx2)Daac/Gt(ROSA)26Sortm1.1(Otx2)Daac
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
involves: 129P2/OlaHsd * C57BL/6 * DBA/2 MGI:4887464
cn9
Gt(ROSA)26Sortm1.1(Otx2)Daac/Gt(ROSA)26Sor+
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
involves: 129P2/OlaHsd * C57BL/6 * DBA/2 MGI:4887465
cn10
Ptentm1Hwu/Ptentm1Hwu
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
involves: 129S4/SvJae * C57BL/6 MGI:4849440
cn11
Kcnj6em1.1Ktaka/Kcnj6em1.1Ktaka
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
involves: C57BL/6J * C57BL/6N MGI:6144037


Genotype
MGI:3689567
hm1
Allelic
Composition
Slc6a3tm1.1(cre)Bkmn/Slc6a3tm1.1(cre)Bkmn
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• homozygous and heterozygous mice are normal and viable




Genotype
MGI:5775427
cn2
Allelic
Composition
Cox10tm1Ctm/Cox10tm1Ctm
Slc6a3tm1.1(cre)Bkmn/?
Genetic
Background
B6.Cg-Cox10tm1Ctm Slc6a3tm1.1(cre)Bkmn
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cox10tm1Ctm mutation (1 available); any Cox10 mutation (4 available)
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• mice exhibit a decline in motor activity and coordination by 2 months of age, maximum decline is reached by 4 months of age
• mice are not able to perform the pole test by 2 months of age, however, treatment with high dose L-DOPA (25 mg/kg) or pioglitazone improves performance
• impaired rotarod performance by 2 months of age, however, treatment with high dose L-DOPA (25 mg/kg) or pioglitazone improves performance
• walking time is decreased on rotarod at 4 and 6 months as compared to younger animals
• decrease in rearing activity by 2 months of age, maximum decline is reached by 4 months of age
• mice move less during nocturnal cycle and in open field test (distance travelled) as compared to controls; treatment with high dose L-DOPA (25 mg/kg) results in hyperactivity and stereotypic movements
• maximum decline in motor performance is reached at 4 months of age

hematopoietic system
• activation of microglial cells in midbrain as detected by Iba1 immunoreactivity
• treatment with pioglitazone for 4 months results in reduction in Iba1 immunoreactivity in midbrain

growth/size/body
• pups are born at a lower body weight than controls and remain at a lower weight throughout life
• administration of pioglitazone increases weight to control levels

immune system
• activation of microglial cells in midbrain as detected by Iba1 immunoreactivity
• treatment with pioglitazone for 4 months results in reduction in Iba1 immunoreactivity in midbrain
• CXCL10 and CCL2 are increased in striatum
• in midbrain, levels of IL6, IL10, CXCL10 and CCL2 trend upward, but do not reach significance
• increase in IL1B in midbrain in 2 month old mice
• IL1B is slightly increased in striatum but does not reach significance

homeostasis/metabolism
• decrease in dopamine and dopamine metabolites (to a lesser extent) in striatum by 2 months of age as compared to controls
• dopamine depletion continues through out life but does not worsen

nervous system
• activation of microglial cells in midbrain as detected by Iba1 immunoreactivity
• treatment with pioglitazone for 4 months results in reduction in Iba1 immunoreactivity in midbrain
• substantial loss of dopaminergic cell bodies in the substantial nigra as measured by reduction of tyrosine hydroxylase (TH) and dopamine transporter (DAT) content
• widespread axonal degeneration in striatum

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Parkinson's disease DOID:14330 OMIM:607688
OMIM:610297
OMIM:613643
OMIM:614251
OMIM:PS168600
J:231810




Genotype
MGI:5292386
cn3
Allelic
Composition
Drd2tm1.1Mrub/Drd2tm1.1Mrub
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
Genetic
Background
B6.Cg-Drd2tm1.1Mrub Slc6a3tm1.1(cre)Bkmn
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Drd2tm1.1Mrub mutation (1 available); any Drd2 mutation (58 available)
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• 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
• 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
• in an open field that is insensitive to quinpirole treatment
• however, habituation is normal
• 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

nervous system
• quinpirole fails to induce a slow hyperpolarizing current in dopaminergic neurons unlike in similarly treated control cells
• however, response to baclofen is normal
• decreased and insensitive to sulpiride
• during train stimulation, mice exhibit supramaximal dopamine release that increases during stimulation that is insensitive to sulpiride unlike in control mice

homeostasis/metabolism
• 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
• mice treated with haloperidol exhibit greater decrease in locomotion compared with similarly treated control mice




Genotype
MGI:5441518
cn4
Allelic
Composition
Gt(ROSA)26Sortm1.1(CAG-COX8A/Dendra2)Dcc/Gt(ROSA)26Sor+
Mfn1tm2Dcc/Mfn1tm2Dcc
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
Genetic
Background
involves: 129 * 129S6/SvEvTac * C57BL/6J * SJL/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1.1(CAG-COX8A/Dendra2)Dcc mutation (1 available); any Gt(ROSA)26Sor mutation (510 available)
Mfn1tm2Dcc mutation (2 available); any Mfn1 mutation (6 available)
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• mice show no abnormal phenotype up to 1 year of age




Genotype
MGI:5441517
cn5
Allelic
Composition
Gt(ROSA)26Sortm1.1(CAG-COX8A/Dendra2)Dcc/Gt(ROSA)26Sor+
Mfn2tm3Dcc/Mfn2tm3Dcc
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
Genetic
Background
involves: 129 * 129S6/SvEvTac * C57BL/6J * SJL/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1.1(CAG-COX8A/Dendra2)Dcc mutation (1 available); any Gt(ROSA)26Sor mutation (510 available)
Mfn2tm3Dcc mutation (2 available); any Mfn2 mutation (20 available)
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 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

growth/size/body
• mutants are significantly smaller than controls by 5 weeks of age
• mutants do not gain weight after 4 weeks of age

behavior/neurological
• mutants are hunched by 5 weeks of age
• severe rearing defect as early as 4 weeks of age
• treatment of mutants with L-DOPA alleviates the motor defects
• 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
• 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

nervous system
• 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
• 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
• dopaminergic neurons remaining have smaller cell bodies and diminished neuronal processes
• dopaminergic neurons exhibit mitochondrial fragmentation and depletion
• retrograde degeneration of substantia nigra pars compacta dopaminergic neurons and to a lesser extent in the mesolimbic pathway
• 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
• mutants show decreased mitochondrial transport along nerve processes

cellular
• dopaminergic neurons exhibit mitochondrial fragmentation and depletion

skeleton

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Parkinson's disease DOID:14330 OMIM:607688
OMIM:610297
OMIM:613643
OMIM:614251
OMIM:PS168600
J:188347




Genotype
MGI:4887467
cn6
Allelic
Composition
Otx2tm6Asim/Otx2tm11Asim
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
Genetic
Background
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Otx2tm11Asim mutation (1 available); any Otx2 mutation (36 available)
Otx2tm6Asim mutation (1 available); any Otx2 mutation (36 available)
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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
• the percentage of GFP+ glyco-Slc6a3 (DAT)+ neurons is higher than in control mice

homeostasis/metabolism
• 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

cellular
• 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
• the percentage of GFP+ glyco-Slc6a3 (DAT)+ neurons is higher than in control mice




Genotype
MGI:4887466
cn7
Allelic
Composition
Gt(ROSA)26Sortm1.1(Otx2)Daac/Gt(ROSA)26Sortm1.1(Otx2)Daac
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
Tg(CAG-Otx2,-GFP)21Asim/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1.1(Otx2)Daac mutation (0 available); any Gt(ROSA)26Sor mutation (510 available)
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
Tg(CAG-Otx2,-GFP)21Asim mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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
• 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

homeostasis/metabolism
• 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

cellular
• 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




Genotype
MGI:4887464
cn8
Allelic
Composition
Gt(ROSA)26Sortm1.1(Otx2)Daac/Gt(ROSA)26Sortm1.1(Otx2)Daac
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1.1(Otx2)Daac mutation (0 available); any Gt(ROSA)26Sor mutation (510 available)
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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
• 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

homeostasis/metabolism
• 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

cellular
• 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




Genotype
MGI:4887465
cn9
Allelic
Composition
Gt(ROSA)26Sortm1.1(Otx2)Daac/Gt(ROSA)26Sor+
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1.1(Otx2)Daac mutation (0 available); any Gt(ROSA)26Sor mutation (510 available)
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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

homeostasis/metabolism
• 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

cellular
• 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




Genotype
MGI:4849440
cn10
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
Genetic
Background
involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (38 available)
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
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

behavior/neurological
N
• no difference in locomotor activity is seen compared to controls during exposure to a novel environment
• mutants exhibit a significant reduction in ipsilateral rotational behavior in response to amphetamine administration after 6OHDA lesioning

nervous system
• 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
• increase in the number of TH positive neurons in the substantia nigra compacta
• increase in the number of dopaminergic neuron dendritic processes in the substantia nigra pars reticulata
• modest but significant enlargement of the caudal striatum
• 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
• hypertrophy of dopamine neurons
• mutant dopamine neurons are protected from 6OHDA induced lesions, fiber loss, and axonal loss in the striatum compared to controls

homeostasis/metabolism
• 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




Genotype
MGI:6144037
cn11
Allelic
Composition
Kcnj6em1.1Ktaka/Kcnj6em1.1Ktaka
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
Genetic
Background
involves: C57BL/6J * C57BL/6N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kcnj6em1.1Ktaka mutation (0 available); any Kcnj6 mutation (14 available)
Slc6a3tm1.1(cre)Bkmn mutation (1 available); any Slc6a3 mutation (47 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• 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

nervous system
• 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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last database update
01/14/2020
MGI 6.14
The Jackson Laboratory