Phenotypes associated with this allele

• Allele Symbol: Snca^tm1Rosl
• Allele Name: targeted mutation 1, Arnon Rosenthal
• Allele ID: MGI:1888382
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Snca^tm1Rosl/Snca^tm1Rosl	B6.129X1-Snca^tm1Rosl	MGI:4415716
hm2	Snca^tm1Rosl/Snca^tm1Rosl	involves: 129X1/SvJ	MGI:3805758
hm3	Snca^tm1Rosl/Snca^tm1Rosl	involves: 129X1/SvJ * C57BL/6	MGI:3720759
cx4	Snca^tm1Rosl/Snca^tm1Rosl Sncg^tm1Vlb/Sncg^tm1Vlb	B6.129-Snca^tm1Rosl Sncg^tm1Vlb	MGI:4417820
cx5	Snca^tm1Rosl/Snca^tm1Rosl Tg(SNCA*A30P)192Rwm/0	B6.Cg-Snca^tm1Rosl Tg(SNCA*A30P)#Rwm	MGI:5543906
cx6	Snca^tm1Rosl/Snca^tm1Rosl Tg(SNCA)OVX37Rwm/0	B6.Cg-Tg(SNCA)OVX37Rwm Snca^tm1Rosl	MGI:5544308
cx7	Snca^tm1Rosl/Snca^tm1Rosl Tg(Prnp-SNCA)7Vle/Tg(Prnp-SNCA)7Vle	involves: 129X1/SvJ * C3H * C57BL/6	MGI:3805760
cx8	Snca^tm1Rosl/Snca^tm1Rosl Tg(Prnp-SNCA*A53T)83Vle/Tg(Prnp-SNCA*A53T)83Vle	involves: 129X1/SvJ * C3H * C57BL/6	MGI:3805759

Genotype
MGI:4415716

hm1

• Allelic Composition: Snca^tm1Rosl/Snca^tm1Rosl
• Genetic Background: B6.129X1-Snca^tm1Rosl

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

nervous system

nervous system phenotype ( J:86439 , J:92213 )

N • at P2, homozygotes display normal numbers of sensory neurons in trigeminal ganglia and L6 lumbar dorsal root ganglia relative to wild-type controls (J:86439)

N • homozygotes exhibit normal morphology and numbers of myelinated A-fibers and unmyelinated C-fibers in adult saphenous nerves relative to wild-type controls (J:86439)

N • in culture, neurons from P2 peripheral (trigeminal and superior cervical) ganglia of mutant mice display the same survival rate as wild-type neurons in the presence of nerve growth factor and, as expected, fail to survive in its absence (J:86439)

N • homozygotes display no gross abnormalities of the nervous system relative to wild-type controls (J:92213)

N • no significant differences in dopamine or its metabolite (DOPAC, 5-HIAA and HVA) levels are noted in the striatum at 9 months of age (J:92213)

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:92213 )

• homozygotes display resistance of SNpc dopaminergic neurons to MPTP neurotoxicity

decreased dopaminergic neuron number ( J:92213 )

• adult homozygotes show a ~20% reduction in the number of tyrosine hydroxylase (TH)-positive dopaminergic neurons in substantia nigra pars compacta (SNpc) but not in ventral tegmental area (VTA) relative to wild-type controls, similar to that observed in adult Sncg^tm1Vlb homozygotes

• however, no significant decrease in the number of TH-positive dopaminergic neurons is observed in SNpc after methyl-phenyl-tetrahydropyridine (MPTP) treatment relative to controls

homeostasis/metabolism

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:92213 )

• homozygotes display resistance of SNpc dopaminergic neurons to MPTP neurotoxicity

behavior/neurological

behavior/neurological phenotype ( J:92213 )

N • homozygotes are behaviorally normal and show no detectable motor dysfunction in either constant speed or accelerating rotarod tests

cellular

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:92213 )

• homozygotes display resistance of SNpc dopaminergic neurons to MPTP neurotoxicity

Genotype
MGI:3805758

hm2

• Allelic Composition: Snca^tm1Rosl/Snca^tm1Rosl
• Genetic Background: involves: 129X1/SvJ

immune system

decreased susceptibility to bacterial infection ( J:138194 )

• mice do not exhibit as much dopamine neuron loss following injection of LPS into the substantia nigra as similarly treated wild-type mice

Genotype
MGI:3720759

hm3

• Allelic Composition: Snca^tm1Rosl/Snca^tm1Rosl
• Genetic Background: involves: 129X1/SvJ * C57BL/6

nervous system

abnormal dopaminergic neuron morphology ( J:60151 )

• when exposed to paired electrical stimuli, striatal brain slices (containing dopamine terminals) from homozygous mice exhibit a faster dopamine release recovery as compared to wild-type

• dopamine discharge and reuptake in response to a single electrical pulse or a train of pulses is comparable to wild-type

behavior/neurological

abnormal locomotor activation ( J:60151 )

• homozygous mice exhibit an attenuated locomotor response after administration of amphetamine as compared to wild-type

• in the absence of amphetamine, locomotor activity in the open field test is comparable to wild-type

homeostasis/metabolism

decreased dopamine level ( J:60151 )

• dopamine content is reduced by 18% in the striatum, however, dopamine content in the ventral midbrain and nucleus accumbens is similar to wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 1		DOID:0060367	OMIM:168601	J:60151

Genotype
MGI:4417820

cx4

• Allelic Composition: Snca^tm1Rosl/Snca^tm1Rosl; Sncg^tm1Vlb/Sncg^tm1Vlb
• Genetic Background: B6.129-Snca^tm1Rosl Sncg^tm1Vlb

nervous system

nervous system phenotype ( J:92213 )

N • double homozygotes are viable, fertile and display no gross abnormalities of the nervous system

N • no significant differences in dopamine or its metabolite (DOPAC, 5-HIAA and HVA) levels are noted in the striatum at 9 months of age

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:92213 )

• similar to single homozygotes, double homozygotes display resistance of SNpc dopaminergic neurons to MPTP neurotoxicity

decreased dopaminergic neuron number ( J:92213 )

• adult double homozygotes show a ~20% reduction in the number of tyrosine hydroxylase (TH)-positive dopaminergic neurons in substantia nigra pars compacta (SNpc) but not in ventral tegmental area (VTA) relative to wild-type controls, similar to that observed in adult single homozygotes

• however, no significant decrease in the number of TH-positive dopaminergic neurons is observed in SNpc after methyl-phenyl-tetrahydropyridine (MPTP) treatment relative to controls

homeostasis/metabolism

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:92213 )

• similar to single homozygotes, double homozygotes display resistance of SNpc dopaminergic neurons to MPTP neurotoxicity

behavior/neurological

behavior/neurological phenotype ( J:92213 )

N • double homozygotes are behaviorally normal and show no detectable motor dysfunction in either constant speed or accelerating rotarod tests

cellular

decreased susceptibility to dopaminergic neuron neurotoxicity ( J:92213 )

• similar to single homozygotes, double homozygotes display resistance of SNpc dopaminergic neurons to MPTP neurotoxicity

Genotype
MGI:5543906

cx5

• Allelic Composition: Snca^tm1Rosl/Snca^tm1Rosl; Tg(SNCA*A30P)192Rwm/0
• Genetic Background: B6.Cg-Snca^tm1Rosl Tg(SNCA*A30P)#Rwm

behavior/neurological

behavior/neurological phenotype ( J:201961 )

N • aged mutants do not exhibit catecholaminergic neuron loss or alpha-synuclein neuropathology and show normal novelty-induced activity, forepaw stride length, activity on the accelerating rotarod, anxiety, immobility times in the tail suspension test, circadian rhythms, and spontaneous alternation in the T-maze

increased locomotor activity ( J:201961 )

• mutants are more active in wheel running during the dark phase, however activity in locomotor cages is normal

homeostasis/metabolism

decreased dopamine level ( J:201961 )

• electrically evoked release of dopamine is reduced in the caudate putamen, but not in the nucleus accumbens compared to single homozygous Snca^tm1Rosl mutants, and show normal norepinephrine release in the stria terminalis

nervous system

abnormal nervous system physiology ( J:201961 )

• mutants are sensitive to the dopaminergic neurotoxin, MPTP, showing nigral and striatal damage, unlike single homozygous Snca^tm1Rosl mutants which show resistance

digestive/alimentary system

digestive/alimentary phenotype ( J:201961 )

N • mutants appear to have normal gastrointestinal function as shown by normal stool water content, stool dry weight and stool frequency

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 1		DOID:0060367	OMIM:168601	J:201961

Genotype
MGI:5544308

cx6

• Allelic Composition: Snca^tm1Rosl/Snca^tm1Rosl; Tg(SNCA)OVX37Rwm/0
• Genetic Background: B6.Cg-Tg(SNCA)OVX37Rwm Snca^tm1Rosl

behavior/neurological

impaired coordination ( J:201991 )

• 18 month old mutants show a reduced latency to fall on the rotarod test and are impaired on the multiple static rods test

• however, no differences in the latency to fall in the inverted screen test is seen

short stride length ( J:201991 )

• reduction in forepaw stride length in 18 month old mutants

digestive/alimentary system

constipation ( J:201991 )

♂ • dry stool weight is increased in males but not females, independent of age; however, stool frequency and stool water content are normal, indicating constipation-like phenotype

homeostasis/metabolism

increased dopamine level ( J:201991 )

• net dopamine content is unchanged in caudate putamen or nucleus accumbens at 3-4 and 12 months of age, however at 18 months of age, dopamine content is greater in the caudate putamen

nervous system

abnormal dopaminergic neuron morphology ( J:201991 )

• vesicles in dopamine axons of the dorsal striatum are more clustered than in controls at 3 months of age; the frequency distribution of intervesicle distance is reduced and vesicles are 3 times less dispersed

loss of dopaminergic neurons ( J:201991 )

• 18 month old mutants exhibit loss of substantia nigra pars compacta dopamine neurons

neuron degeneration ( J:201991 )

• 18 month old mutants exhibit loss of substantia nigra pars compacta dopamine neurons

• however, aggregation of alpha-synuclein is not seen in the substantia nigra pars compacta or striatum

abnormal neuron physiology ( J:201991 )

• substantia nigra pars compacta dopamine neurons exhibit age-dependent reductions (almost 30%) in firing rates in vivo

abnormal synaptic dopamine release ( J:201991 )

• in the dorsal striatum, mean peak extracellular concentrations of dopamine evoked by single electrical pulses across distributed recording sites are on average about 30% lower than in controls; this reduced release is seen from a young age of 3-4 months before the loss of dopamine neurons and persists throughout their lifespan

• greatest deficits in dopamine release are seen in the dorsal and lateral striatum

• the dopamine release deficit persists in the presence of nicotinic receptor blockade by dihydro-beta-erythroidine

• dopamine uptake kinetics are normal and norepinephrine and 5-hydroxytryptamine axonal release are normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 1		DOID:0060367	OMIM:168601	J:201991

Genotype
MGI:3805760

cx7

• Allelic Composition: Snca^tm1Rosl/Snca^tm1Rosl; Tg(Prnp-SNCA)7Vle/Tg(Prnp-SNCA)7Vle
• Genetic Background: involves: 129X1/SvJ * C3H * C57BL/6

nervous system

astrocytosis ( J:138194 )

• following injection of LPS into the substantia nigra

loss of dopaminergic neurons ( J:138194 )

• following injection of LPS into the substantia nigra, mice exhibit an increased loss of dopaminergic neurons that is associated with insoluble and aggregated SNCA compared to in Snca^tm1Rosl homozygotes

• following culture with LPS, dopaminergic neurons loss is increased compared to in cultures from Snca^tm1Rosl homozygotes

• loss of dopamine neurons following injection of LPS into the substantia nigra is mediated by microglial-derived nitric oxide and superoxideloss of dopamine neurons following injection of LPS into the substantia nigra is mediated by microglial-derived nitric oxide and superoxide

• however, loss of dopamine neurons is not due to an abnormal inflammatory response following injection of LPS into the substantia nigra

immune system

abnormal response to infection ( J:138194 )

• following injection of LPS into the substantia nigra, mice exhibit a decreased loss of dopaminergic neurons compared to in Snca^tm1Rosl Tg(Prnp-SNCA*A53T)83Vle homozygotes but increased relative to in Snca^tm1Rosl homozygotes

Genotype
MGI:3805759

cx8

• Allelic Composition: Snca^tm1Rosl/Snca^tm1Rosl; Tg(Prnp-SNCA*A53T)83Vle/Tg(Prnp-SNCA*A53T)83Vle
• Genetic Background: involves: 129X1/SvJ * C3H * C57BL/6

nervous system

astrocytosis ( J:138194 )

• following injection of LPS into the substantia nigra

loss of dopaminergic neurons ( J:138194 )

• following injection of LPS into the substantia nigra, mice exhibit an increased loss of dopaminergic neurons that is associated with insoluble and aggregated SNCA compared to in Snca^tm1Rosl Tg(Prnp-SNCA)7Vle and Snca^tm1Rosl homozygotes

• however, loss of dopamine neurons is not due to an abnormal inflammatory response following injection of LPS into the substantia nigra

immune system

increased susceptibility to bacterial infection ( J:138194 )

• following injection of LPS into the substantia nigra, mice exhibit an increased loss of dopaminergic neurons compared to in Snca^tm1Rosl Tg(Prnp-SNCA)7Vle and Snca^tm1Rosl homozygotes