Phenotypes associated with this allele

• Allele Symbol: Vps35⁺
• Allele Name: wild type
• Allele ID: MGI:2435907
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Vps35^Gt(RRK261)Byg/Vps35^+	B6.129P2-Vps35^Gt(RRK261)Byg	MGI:5695247
ht2	Vps35^tm1.1Mjff/Vps35^+	B6.Cg-Vps35^tm1.1Mjff	MGI:7378804
ht3	Vps35^em1(IMPC)H/Vps35^+	C57BL/6N-Vps35^em1(IMPC)H/H	MGI:6408760
ht4	Vps35^tm1.1Hlw/Vps35^+	involves: 129S/SvEv * C57BL/6J	MGI:7466182
ht5	Vps35^tm1.2Mjff/Vps35^+	involves: C57BL/6	MGI:5526855
cx6	Vps35^Gt(RRK261)Byg/Vps35^+ Tg(APPSWE)2576Kha/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5306777

Genotype
MGI:5695247

ht1

• Allelic Composition: Vps35^{Gt(RRK261)Byg}/Vps35⁺
• Genetic Background: B6.129P2-Vps35^{Gt(RRK261)Byg}

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

behavior/neurological

decreased vertical activity ( J:225806 )

• rearing frequency is decreased by 35.6% and 82.2% in 12- and 18- month old mice, respectively

decreased locomotor activity ( J:225806 )

• in the open field, total distance and velocity of 12- and 18-month old mice is reduced

• however, performance in the rotarod and gait tests is normal

homeostasis/metabolism

decreased dopamine level ( J:225806 )

• dopamine levels are reduced in the striatum and ventral midbrain at 6 month or older mutants

• ratios of 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine or 3,4-dihydroxyphenylacetic acid (HVA)/dopamine are much higher in 12 month old mutant striatum compared to controls

• however, 5-HT levels are normal

nervous system

abnormal dopaminergic neuron morphology ( J:225806 )

• TH+ neurons exhibit disturbed and decreased fibers/processes in substantia nigra pars compacta of aged mice

loss of dopaminergic neurons ( J:225806 )

• decrease in the number of TH+ neurons in aged (12 months) mice, with an approximate 20% loss of TH+ somas in the substantia nigra pars compacta

alpha-synuclein inclusion body ( J:225806 )

• mice show age-dependent accumulation of alpha-synuclein in in substantia nigra pars compacta-dopamine neurons

• both monomeric and oligomeric, or phosphorylated and unphosphorylated, species of alpha-synuclein are increased in mice older than 6 months, with an increase only in the ventral midbrain but not in the hippocampus

cellular

abnormal lysosome morphology ( J:225806 )

• Lamp1-positive late endosomes/early lysosomes appear enlarged in dopamine neurons

• Lamp2-positive vesicles appear smaller in size in dopamine neurons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 17		DOID:0060897	OMIM:614203	J:225806

Genotype
MGI:7378804

ht2

• Allelic Composition: Vps35^tm1.1Mjff/Vps35⁺
• Genetic Background: B6.Cg-Vps35^tm1.1Mjff

homeostasis/metabolism

abnormal nervous system dopamine level ( J:274797 )

• Increased dopamine release in dorsolateral striatal slices as measured by fast scan cyclic voltammetry; in heterozygote increase is less than in homozygote, but higher than in wild-type

• Decay time of dopamine transient is slower in dorsolateral striatal slices

• Increased dopamine turnover as measured by ration of dopamine metabolites to dopamine

• In response to a D2 agonist, quinpirole, dorsolateral striatal slices exhibit a more rapid inhibition of dopamine release

nervous system

abnormal nervous system dopamine level ( J:274797 )

• Increased dopamine release in dorsolateral striatal slices as measured by fast scan cyclic voltammetry; in heterozygote increase is less than in homozygote, but higher than in wild-type

• Decay time of dopamine transient is slower in dorsolateral striatal slices

• Increased dopamine turnover as measured by ration of dopamine metabolites to dopamine

• In response to a D2 agonist, quinpirole, dorsolateral striatal slices exhibit a more rapid inhibition of dopamine release

Genotype
MGI:6408760

ht3

• Allelic Composition: Vps35^em1(IMPC)H/Vps35⁺
• Genetic Background: C57BL/6N-Vps35^em1(IMPC)H/H

Data Sources

IMPC Data for Vps35

behavior/neurological

abnormal gait ( J:211773 )

♂

IMPC - HAR

vision/eye

abnormal retina morphology ( J:211773 )

♂

IMPC - HAR

Genotype
MGI:7466182

ht4

• Allelic Composition: Vps35^tm1.1Hlw/Vps35⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6J

behavior/neurological

decreased locomotor activity ( J:329507 )

• at age 16 months

• normal at age 12 months

bradykinesia ( J:329507 )

• at age 16 months

• normal at age 12 months

slow movement ( J:329507 )

• at age 16 months

• normal at age 12 months

nervous system

nervous system phenotype ( J:329507 )

N • normal number of neurons in striatum and cerebral cortex at age 16 months

abnormal substantia nigra pars compacta morphology ( J:329507 )

• reduced number of tyrosine hydroxylase (TH)-positive dopaminergic neurons at age 16 months

• reduced number of tyrosine hydroxylase (TH)-positive dopaminergic nigrostriatal terminals at age 16 months

• normal number of tyrosine hydroxylase (TH)-positive dopaminergic neurons at age 12 months

cellular

abnormal mitochondrial shape ( J:329507 )

• truncated, shortened and fragmented in (TH)-positive dopaminergic substantia nigra pars compacta neurons at age 16 months

decreased mitochondrial size ( J:329507 )

• in (TH)-positive dopaminergic substantia nigra pars compacta neurons at age 16 months

oxidative stress ( J:329507 )

• in mitochondria of (TH)-positive dopaminergic substantia nigra pars compacta neurons at age 16 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 17		DOID:0060897	OMIM:614203	J:329507

Genotype
MGI:5526855

ht5

• Allelic Composition: Vps35^tm1.2Mjff/Vps35⁺
• Genetic Background: involves: C57BL/6

normal phenotype

no abnormal phenotype detected ( J:101977 )

• viable and fertile

Genotype
MGI:5306777

cx6

• Allelic Composition: Vps35^{Gt(RRK261)Byg}/Vps35⁺; Tg(APPSWE)2576Kha/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

Increase of amyloid beta deposits and amyloid beta 40 in the hippocampus and cortex of Vps35^{Gt(RRK261)Byg}/Vps35⁺ Tg(APPSWE)2576Kha/0 mice

nervous system

nervous system phenotype ( J:178937 )

N • mice exhibit normal paired-pulse facilitation and inhibitory synaptic transmission

amyloid beta deposits ( J:178937 )

• in the hippocampus and cerebral cortex

• greater accumulation than in Tg(APPSWE)2576Kha mice

impaired synaptic plasticity ( J:178937 )

• accelerated compared to in Tg(APPSWE)2576Kha mice

abnormal excitatory postsynaptic potential ( J:178937 )

• field excitatory postsynaptic potential slopes in the CA1 and dentate gyrus are reduced compared to in either single heterozygotes

reduced AMPA-mediated synaptic currents ( J:178937 )

• mice exhibit reduced AMPA and NMDA receptor-mediated miniature excitatory postsynaptic currents in CA1 pyramidal neurons compared with control mice

reduced NMDA-mediated synaptic currents ( J:178937 )

• mice exhibit reduced AMPA and NMDA receptor-mediated miniature excitatory postsynaptic currents in CA1 pyramidal neurons compared with control mice

reduced long-term potentiation ( J:178937 )

• in the CA1 at 2 months

• worsened at 4 months in the CA1

• however, long term potentiation in the dentate gyrus is normal

abnormal miniature excitatory postsynaptic currents ( J:178937 )

• mice exhibit reduced AMPA and NMDA receptor-mediated miniature excitatory postsynaptic currents in CA1 pyramidal neurons compared with control mice

decreased post-tetanic potentiation ( J:178937 )

• at 4 months in the CA1

behavior/neurological

abnormal spatial learning ( J:178937 )

• in a Morris water maze, mice exhibit increased latencies to finding the hidden platform and in pathway length compared with either single heterozygote

• deficits increase with age

homeostasis/metabolism

amyloid beta deposits ( J:178937 )

• in the hippocampus and cerebral cortex

• greater accumulation than in Tg(APPSWE)2576Kha mice